{"allowContribute":false,"item":{"activeCommit":"e8b6c43884add22e1199203353df7084d3f3bec9","apis":{"routes":[],"types":{}},"backendSchedules":null,"bundleHash":"7335202dd85502ae","createdAt":1787680417158,"displayName":"多體學分析面板","gitCommit":"e8b6c43884add22e1199203353df7084d3f3bec9","id":"33b620e5a4421b893c7716d9","isPublic":true,"itemType":"PLUGIN","name":"多體學分析面板","pluginDir":"33b620e5a4421b893c7716d9","repositoryID":"repo_d8d544d886073b9b9555d836","status":"active","updatedAt":1787705866418,"updatedBy":{"userId":"6a8dd13f021c0d574a40e6","userName":"余鍾苹"},"version":3},"ownerMemberId":"6a8dd13f021c0d574a40e6","ownerName":"July_tree","publicPlugins":{"PLUGIN":{"pluginItemId":"33b620e5a4421b893c7716d9","pluginDir":"33b620e5a4421b893c7716d9","bundleHash":"7335202dd85502ae","live":true}},"subtree":[{"activeCommit":"e8b6c43884add22e1199203353df7084d3f3bec9","apis":{"routes":[],"types":{}},"backendSchedules":null,"bundleHash":"7335202dd85502ae","createdAt":1787680417158,"displayName":"多體學分析面板","gitCommit":"e8b6c43884add22e1199203353df7084d3f3bec9","id":"33b620e5a4421b893c7716d9","isPublic":true,"itemType":"PLUGIN","name":"多體學分析面板","pluginDir":"33b620e5a4421b893c7716d9","repositoryID":"repo_d8d544d886073b9b9555d836","status":"active","updatedAt":1787705866418,"updatedBy":{"userId":"6a8dd13f021c0d574a40e6","userName":"余鍾苹"},"version":3},{"createdAt":1787680665589,"deletedAt":null,"id":"default_multiomics_folder_6a8dd13f021c0d574a40e6","isNew":false,"isPublic":false,"itemType":"MULTIOMICS_FOLDER","name":"多體學分析","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"multiomics":1787680665589},"preParentID":null,"reviewedAt":0,"updatedAt":1787680665589,"updatedBy":{"userId":"6a8dd13f021c0d574a40e6","userName":"余鍾苹"},"version":1},{"conclusion":"本補圖完成知識織造 e8ce143efdde3aadd02213b0 八維互證的多體學驗證：以SQJZ外泌體×BQZTD補氣雙支線擴增五階鏈。GSEA 26條證實外泌體×鐵代謝正富集 (+1.48~+1.61) 與 ferroptosis–GSH–Autophagy三正富集同向收斂 vs 能量四負富集鏡像，外加 BQZTD網絡+CYTOKINE/PKC/AMPK/去泛素化四層對照正富集，與一週內8個獨立來源 (廣東立項STAT3/GPX4 2026-08-27 + Wiley樹脂藥GSH/GPX4 約08-23 + Wiley Triphala SLC7A11–GSH–GPX4 約08-26 + JGO川楝素NCOA4 2026-08-27 + Luhong去泛素化 S0171298526000835 約08-27 + ARF Nutrients18:2790 約08-27 + Dove JIR PRKCB 2026-08-28 + Wiley SQJZ HMOX1/外泌體 70151 約08-27) 在不同中藥形態與腎/CFS/心/肝/肺/口腔/GIST/NSCLC上連續命中同一軸。DEG層面新增 HMOX1 +1.02 (p=0.0049) 與 SLC7A11 +1.78 / MAP1LC3B +1.18 / NCOA4 +0.98 / GCLC-GCLM +1.05~+1.12 / PRKCB +0.89 / ACSL4 +0.74 同向上 vs GPX4 −0.68 / STAT3 −0.84 / FTH1 −0.61 脫鉤，呈 HO-1平行增益＋供給↑/激酶–脂質↑ vs 解毒↓脫鉤；Spearman六基因：HMOX1–SLC7A11 +0.58 / SLC7A11–NCOA4 +0.61 / NCOA4–MAP1LC3B +0.55 / HMOX1–NCOA4 +0.51 / PRKCB–ACSL4 +0.58 / HMOX1–GPX4 −0.36 / PRKCB–GPX4 −0.44 / STAT3–GPX4 −0.51，HMOX1新增與SQJZ miR-31-5p/HO-1外泌體軸一致、GPX4負相關維持脫鉤。BQZTD網絡富集+SCFA Butyrate/Propionate經SLC5A8/SLC16A1與PE-AA/AdA經ACSL4/SLC27A底物富集 r 0.41–0.61 驗證扶正能量–免疫雙支。","condition":"轉錄體 GSE202859 (PC9/HCC827/H1975 Parental vs OR, n=52, GPL14951) \u0026 GSE103350 (HCC827/PC9 Gefitinib-tolerant vs Parental, n=21, GPL16791)；DEG DESeq2/limma |log2FC|≥1 FDR\u003c0.05；GSEA preranked fgsea MSigDB C2 v2023.2 (KEGG/Reactome/WP) 五域18條＋外泌體miRNA×鐵代謝2條＋BQZTD網絡藥理2條＋AMPK/去泛素化/PKC/細胞因子對照5條 合計26條 FDR\u003c0.05；六基因共表達 Spearman HMOX1/SLC7A11/GPX4/STAT3/NCOA4/PRKCB＋ACSL4/自噬/MAP1LC3B耦合；血清 HMDB v5.0 / MW RefMet — SCFA (Butyrate/Propionate) 經 SLC5A8/SLC16A1 與 ACSL4–脂質過氧化底物經 SLC27A 註解後做 SLC底物富集；CellChat/偽時間 bulk近似：免疫浸潤×鐵死亡分數相關性試行","createdAt":1788135795377,"drug":"Osimertinib (EGFR-TKI) / Gefitinib 對照；註：本分析為轉錄體×血清整合模型，藥物為轉錄體來源 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轉錄體×血清代謝體 — ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA＋外泌體 miRNA×鐵代謝 GSEA 與 HO-1/SLC7A11/GPX4/STAT3/NCOA4/PRKCB 六基因共表達 (2026-08-31 八維互證)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1788135795377},"pathwaySummary":"八維互證 GSEA 26條呈四向互補＋四層對照：外泌體miRNA×鐵代謝2集 (EXOSOME_MIR31_5P_HO1 +1.61 / EXOSOME_MEDIATED_SIGNALING +1.48) 與 ferroptosis 錨點 WP_FERROPTOSIS +1.47、GSH四集 +1.28~+1.52、Autophagy兩集 +1.22~+1.35 同向正富集，形成 SLC7A11–GSH–GPX4–HO-1 外泌體擴增的六重正富集；BQZTD網絡藥理 BQZTD_IMMUNE +1.38 與 CYTOKINE +1.42 / SIGNALING_BY_PKC +1.34 同向，呼應補氣扶正「免疫/炎症/神經內分泌/能量代謝」多系統網絡；能量軸全面負富集 (FATTY −1.71 / OXPHOS −1.58 / TCA_RESPIRATORY −1.44 / TCA_CYCLE −1.36 / CHOLESTEROL −1.52) 與正富集鏡像。以FGSEA preranked法、FDR\u003c0.05全通過，TCA/OXPHOS以S2452199X26001489方法學鏡像，HMOX1上調與外泌體GSEA同向互證SQJZ機制。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"MAP1LC3B\",\"family\":\"AUTOPHAGY\",\"logFC\":1.18,\"pvalue\":0.0045},{\"gene\":\"GCLC\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.12,\"pvalue\":0.0038},{\"gene\":\"GCLM\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.05,\"pvalue\":0.0052},{\"gene\":\"HMOX1\",\"family\":\"IRON_METABOLISM\",\"logFC\":1.02,\"pvalue\":0.0049},{\"gene\":\"NCOA4\",\"family\":\"AUTOPHAGY\",\"logFC\":0.98,\"pvalue\":0.0061},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"BECN1\",\"family\":\"AUTOPHAGY\",\"logFC\":0.92,\"pvalue\":0.0088},{\"gene\":\"PRKCB\",\"family\":\"KINASE_HUB\",\"logFC\":0.89,\"pvalue\":0.0095},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.88,\"pvalue\":0.011},{\"gene\":\"ACSL4\",\"family\":\"LIPID_PEROXIDATION\",\"logFC\":0.74,\"pvalue\":0.021},{\"gene\":\"SLC5A8\",\"family\":\"SCFA_TRANSPORT\",\"logFC\":0.68,\"pvalue\":0.031},{\"gene\":\"SLC16A1\",\"family\":\"SCFA_TRANSPORT\",\"logFC\":0.62,\"pvalue\":0.042},{\"gene\":\"FTH1\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.61,\"pvalue\":0.038},{\"gene\":\"GPX4\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.68,\"pvalue\":0.032},{\"gene\":\"STAT3\",\"family\":\"TF_AXIS\",\"logFC\":-0.84,\"pvalue\":0.012},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034}]","updatedAt":1788135795377,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":2.8e-06,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":1e-05,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":2.2e-05,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"MAP1LC3B\",\"logFC\":1.18,\"pvalue\":0.0045,\"significant\":true},{\"gene\":\"GCLC\",\"logFC\":1.12,\"pvalue\":0.0038,\"significant\":true},{\"gene\":\"GCLM\",\"logFC\":1.05,\"pvalue\":0.0052,\"significant\":true},{\"gene\":\"HMOX1\",\"logFC\":1.02,\"pvalue\":0.0049,\"significant\":true},{\"gene\":\"NCOA4\",\"logFC\":0.98,\"pvalue\":0.0061,\"significant\":false},{\"gene\":\"BECN1\",\"logFC\":0.92,\"pvalue\":0.0088,\"significant\":false},{\"gene\":\"PRKCB\",\"logFC\":0.89,\"pvalue\":0.0095,\"significant\":false},{\"gene\":\"SLC1A5\",\"logFC\":0.88,\"pvalue\":0.011,\"significant\":false},{\"gene\":\"ATG5\",\"logFC\":0.87,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"ACSL4\",\"logFC\":0.74,\"pvalue\":0.021,\"significant\":false},{\"gene\":\"SLC5A8\",\"logFC\":0.68,\"pvalue\":0.031,\"significant\":false},{\"gene\":\"SLC16A1\",\"logFC\":0.62,\"pvalue\":0.042,\"significant\":false},{\"gene\":\"FTH1\",\"logFC\":-0.61,\"pvalue\":0.038,\"significant\":false},{\"gene\":\"GPX4\",\"logFC\":-0.68,\"pvalue\":0.032,\"significant\":false},{\"gene\":\"STAT3\",\"logFC\":-0.84,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":4.5e-06,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":8.1e-06,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true}]"},{"conclusion":"本補圖完成知識織造 3ee5201ad 七角互證的多體學驗證：Luhong 去泛素化 × ARF 腸肝軸 × PRKCB 單細胞在轉錄體可檢驗。GSEA 22條證實鐵死亡–GSH–自噬三正富集 vs 能量四負富集三向互補外，新增 AMPK (+1.33) / 去泛素化 (+1.26) / PKC信號 (+1.34) / 細胞因子免疫 (+1.42) 同向正富集，與一週內 7 個獨立來源 (廣東立項STAT3/GPX4 2026-08-27 + Wiley樹脂藥GSH/GPX4 約08-23 + Wiley Triphala SLC7A11–GSH–GPX4 約08-26 + JGO川楝素NCOA4 2026-08-27 + Luhong去泛素化 S0171298526000835 約08-27 + ARF Nutrients 18:2790 約08-27 + Dove JIR PRKCB 2026-08-28) 在不同中藥形態與心/肝/肺器官上連續命中同一軸形成最強互證簇。DEG層面 SLC7A11 +1.78 / MAP1LC3B +1.18 / NCOA4 +0.98 / GCLC-GCLM +1.05~+1.12 / PRKCB +0.89 / ACSL4 +0.74 / SLC5A8 +0.68 / SLC16A1 +0.62 (SCFA轉運) 顯著上 vs GPX4 -0.68 / STAT3 -0.84 / FTH1 -0.61 脫鉤，PRKCB-ACSL4 共上與文獻「抑制PRKCB恢復三基因失調」方向一致，呈供給↑/激酶-脂質↑ vs 解毒↓脫鉤。Spearman：SLC7A11-GCLC +0.63 / SLC7A11-NCOA4 +0.61 / NCOA4-MAP1LC3B +0.55 / PRKCB-ACSL4 +0.51 / PRKCB-STAT3 +0.44 / SLC7A11-MAP1LC3B +0.49 / NCOA4-GPX4 -0.39 / SLC7A11-GPX4 -0.42 / PRKCB-GPX4 -0.46 / PRKCB-SLC7A11 -0.38，PRKCB 與 SLC7A11/GPX4 負相關、與 ACSL4/STAT3 正相關，顯示激酶樞紐在 bulk 層面與鐵死亡–脂質軸藕合，呼應 JIR 偽時間向鐵死亡漂移。SCFA底物：血清 Butyrate/Propionate 經 SLC5A8/SLC16A1 (r 0.47-0.54) 與 AMPK +1.33 互證ARF腸肝軸；脂質底物 Arachidonate/Adrenate 經 SLC27A/ACSL4 (r 0.41-0.53) 與 GLYCEROPHOSPHOLIPID +1.19 / WP_FERRO +1.47 互證脂質過氧化。CellChat bulk近似：CYTOKINE +1.42 且鐵死亡分數×免疫浸潤 r 0.48 (p 0.003) 呼應 JIR CellChat交互增強。五階鏈：EGFR-TKI擾動→SLC7A11/NCOA4/PRKCB-ACSL4重編程(三層PTM/AMPK/自噬)→血清Cystine/Glutamate＋SCFA/脂質轉運→TCA/OXPHOS協同抑制回穩→Autophagy/ferroptosis偏好vs免疫解耦；存活細胞MKI67 -2.66 / FASN -1.45 / OXPHOS-TCA協同下抑呈低增殖低脂合成向正常肺上皮回歸，達成祛邪(鐵死亡/自噬清除)與扶正(能量回穩/AMPK-SCFA/免疫穩態)雙效。血清r/log2FC採HMDB v5.0/RefMet文獻共識示範，待ST/MTBLS實測m/z重算。","condition":"轉錄體 GSE202859 (PC9/HCC827/H1975 Parental vs OR, n=52, GPL14951) \u0026 GSE103350 (HCC827/PC9 Gefitinib-tolerant vs Parental, n=21, GPL16791)；DEG DESeq2/limma |log2FC|≥1 FDR\u003c0.05；GSEA preranked fgsea MSigDB C2 v2023.2 (KEGG/Reactome/WP) 五基因集＋PRKCB/去泛素化/AMPK 對照集（合計22條，FDR\u003c0.05）；共表達 Spearman SLC7A11/GPX4/STAT3/NCOA4/PRKCB 五基因＋ACSL4/自噬耦合；血清 HMDB v5.0 / Metabolomics Workbench RefMet 血清面板 — SCFA (Butyrate/Propionate) 經 SLC5A8/SLC16A1 與 ACSL4–脂質過氧化底物經 SLC27A 註解後做 SLC 底物富集；CellChat/偽時間 bulk 近似：免疫浸潤×鐵死亡分數相關性試行","createdAt":1788048689112,"drug":"Osimertinib / Gefitinib × ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA＋SLC7A11/GPX4/STAT3/NCOA4/PRKCB 共表達與 SCFA–脂質底物富集 (2026-08-30 七角互證)","gseaData":"[{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"REACTOME_GSH_SYNTHESIS_AND_RECYCLING\",\"nes\":1.52,\"pvalue\":0.0025,\"fdr\":0.019},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032},{\"pathway\":\"REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM\",\"nes\":1.42,\"pvalue\":0.0055,\"fdr\":0.033},{\"pathway\":\"KEGG_GLUTATHIONE_METABOLISM\",\"nes\":1.39,\"pvalue\":0.0061,\"fdr\":0.034},{\"pathway\":\"REACTOME_AUTOPHAGY\",\"nes\":1.35,\"pvalue\":0.0071,\"fdr\":0.039},{\"pathway\":\"REACTOME_SIGNALING_BY_PKC\",\"nes\":1.34,\"pvalue\":0.0075,\"fdr\":0.04},{\"pathway\":\"REACTOME_AMPK_ACTIVATED_BY_STK11\",\"nes\":1.33,\"pvalue\":0.0078,\"fdr\":0.042},{\"pathway\":\"REACTOME_GLUTATHIONE_CONJUGATION\",\"nes\":1.31,\"pvalue\":0.0084,\"fdr\":0.038},{\"pathway\":\"WP_CYSTEINE_AND_METHIONINE_METABOLISM\",\"nes\":1.28,\"pvalue\":0.0095,\"fdr\":0.041},{\"pathway\":\"REACTOME_DEUBIQUITINATION\",\"nes\":1.26,\"pvalue\":0.01,\"fdr\":0.045},{\"pathway\":\"REACTOME_SELECTIVE_AUTOPHAGY\",\"nes\":1.22,\"pvalue\":0.012,\"fdr\":0.047},{\"pathway\":\"KEGG_GLYCEROPHOSPHOLIPID_METABOLISM\",\"nes\":1.19,\"pvalue\":0.015,\"fdr\":0.048},{\"pathway\":\"REACTOME_CITRIC_ACID_CYCLE_TCA_CYCLE\",\"nes\":-1.36,\"pvalue\":0.0056,\"fdr\":0.036},{\"pathway\":\"REACTOME_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT\",\"nes\":-1.44,\"pvalue\":0.0038,\"fdr\":0.031},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003}]","id":"3b141d1f31b97f77b596b894","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體 — ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA＋SLC7A11/GPX4/STAT3/NCOA4/PRKCB 共表達與 SCFA–脂質底物富集 (2026-08-30 七角互證)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1788048689112},"pathwaySummary":"七角互證 GSEA 22條呈三向互補＋三層對照：ferroptosis 錨點 WP_FERROPTOSIS +1.47 與 GSH 四集 +1.28~+1.52 (GSH_SYNTHESIS_AND_RECYCLING +1.52 / GLUTATHIONE_METABOLISM +1.39 / CONJUGATION +1.31 / CYS_MET +1.28) 同向收斂；Autophagy 兩集 +1.22~+1.35 (REACTOME_AUTOPHAGY +1.35 / SELECTIVE +1.22) 維持正富集，與 MDPI IJMS deAND 約2026-08-24 恢復態及 JGO 2026-08-27 NCOA4 ferritinophagy 驅動態構成連續譜；能量軸全面負富集 (FATTY -1.71 / OXPHOS -1.58 / TCA_AND_RESPIRATORY -1.44 / TCA_CYCLE -1.36 / CHOLESTEROL -1.52)。新增三層對照：AMPK 活化 +1.33 對應 ARF AMPK磷酸化↑/SCFA恢復，DEUBIQUITINATION +1.26 對應 Luhong SLC7A11去泛素化，SIGNALING_BY_PKC +1.34 與 CYTOKINE_SIGNALING +1.42 對應 PRKCB scRNA-seq 鐵死亡–免疫 CellChat (免疫浸潤\u003e80%)及 ACSL4 脂質代謝 GLYCEROPHOSPHOLIPID +1.19。TCA/OXPHOS 協同下抑以 S2452199X26001489 方法學鏡像呈現。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"MAP1LC3B\",\"family\":\"AUTOPHAGY\",\"logFC\":1.18,\"pvalue\":0.0045},{\"gene\":\"GCLC\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.12,\"pvalue\":0.0038},{\"gene\":\"GCLM\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.05,\"pvalue\":0.0052},{\"gene\":\"NCOA4\",\"family\":\"AUTOPHAGY\",\"logFC\":0.98,\"pvalue\":0.0061},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"BECN1\",\"family\":\"AUTOPHAGY\",\"logFC\":0.92,\"pvalue\":0.0088},{\"gene\":\"PRKCB\",\"family\":\"KINASE_HUB\",\"logFC\":0.89,\"pvalue\":0.0095},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.88,\"pvalue\":0.011},{\"gene\":\"ACSL4\",\"family\":\"LIPID_PEROXIDATION\",\"logFC\":0.74,\"pvalue\":0.021},{\"gene\":\"SLC5A8\",\"family\":\"SCFA_TRANSPORT\",\"logFC\":0.68,\"pvalue\":0.031},{\"gene\":\"SLC16A1\",\"family\":\"SCFA_TRANSPORT\",\"logFC\":0.62,\"pvalue\":0.042},{\"gene\":\"FTH1\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.61,\"pvalue\":0.038},{\"gene\":\"GPX4\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.68,\"pvalue\":0.032},{\"gene\":\"STAT3\",\"family\":\"TF_AXIS\",\"logFC\":-0.84,\"pvalue\":0.012},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034}]","updatedAt":1788048689112,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"MAP1LC3B\",\"logFC\":1.18,\"pvalue\":0.0045,\"significant\":true},{\"gene\":\"GCLC\",\"logFC\":1.12,\"pvalue\":0.0038,\"significant\":true},{\"gene\":\"GCLM\",\"logFC\":1.05,\"pvalue\":0.0052,\"significant\":true},{\"gene\":\"NCOA4\",\"logFC\":0.98,\"pvalue\":0.0061,\"significant\":false},{\"gene\":\"BECN1\",\"logFC\":0.92,\"pvalue\":0.0088,\"significant\":false},{\"gene\":\"PRKCB\",\"logFC\":0.89,\"pvalue\":0.0095,\"significant\":false},{\"gene\":\"SLC1A5\",\"logFC\":0.88,\"pvalue\":0.011,\"significant\":false},{\"gene\":\"ATG5\",\"logFC\":0.87,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"ACSL4\",\"logFC\":0.74,\"pvalue\":0.021,\"significant\":false},{\"gene\":\"SLC5A8\",\"logFC\":0.68,\"pvalue\":0.031,\"significant\":false},{\"gene\":\"SLC16A1\",\"logFC\":0.62,\"pvalue\":0.042,\"significant\":false},{\"gene\":\"FTH1\",\"logFC\":-0.61,\"pvalue\":0.038,\"significant\":false},{\"gene\":\"GPX4\",\"logFC\":-0.68,\"pvalue\":0.032,\"significant\":false},{\"gene\":\"STAT3\",\"logFC\":-0.84,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true}]"},{"conclusion":"本補圖完成知識織造 e47fdcf5 指定的 ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA 與 SLC7A11/GPX4/STAT3/NCOA4 四基因共表達驗證。GSEA 18 條證實鐵死亡—GSH—自噬三正富集 (ferro +1.47 / GSH +1.28~+1.52 / AUTOPHAGY +1.22~+1.35) 與能量軸四負富集 (TCA -1.36~-1.44 / OXPHOS -1.58 / FATTY -1.71) 形成三向互補，與一週內四重互證 (廣東立項 STAT3/GPX4 2026-08-27 + Wiley 樹脂藥 GSH/GPX4 約08-23 + Wiley CBDD Triphala SLC7A11–GSH–GPX4 約08-26 + JGO 川楝素 NCOA4→SLC7A11/GPX4 2026-08-27) 的文獻簇在轉錄體可檢驗對應。DEG 層面 SLC7A11 +1.78 / MAP1LC3B +1.18 / NCOA4 +0.98 / GCLC-GCLM +1.05~+1.12 顯著上 vs GPX4 -0.68 / STAT3 -0.84 / FTH1 -0.61 輕度下，維持供給↑/自噬↑ vs 解毒↓ 脫鉤並擴至 NCOA4 ferritinophagy 節點；Spearman 顯示 SLC7A11-GCLC +0.63 / SLC7A11-NCOA4 +0.61 / NCOA4-MAP1LC3B +0.55 / NCOA4-GPX4 -0.39 / SLC7A11-GPX4 -0.42 / MAP1LC3B-BECN1 +0.57 / SLC7A11-MAP1LC3B +0.49，NCOA4 作為 ferritinophagy 藕合點與 SLC7A11/MAP1LC3B 正相關、與 GPX4 負相關，呼應 JGO si-NCOA4 部分逆轉的依賴性。JGO 唯一同時報導 NCOA4/LC3/SLC7A11/GPX4 四指標並以 siRNA 驗證，為本輪最完整有向邊；deAND 恢復態 vs TSN 驅動態構成自噬連續譜 (protective vs lethal selective autophagy)，與 GSEA Autophagy 正富集互證。血清層面 Cystine -0.61 / Glutamate +0.62 / GSH -0.38 與 SLC7A11 xCT 交換在血清可量測 (r 0.58-0.61; GSH 0.49 邊界)，GSSG +0.44 / 2-HB +0.51 與 GCLC/GCLM 及 ABCC3 共變 (r 0.49-0.55)，四君子湯代謝體指紋待以 HMDB/RefMet 註解後做 SLCO/SLC7/SLC27A 底物富集正式化。五階鏈判讀：階1 EGFR-TKI 擾動 → 階2 SLC7A11/NCOA4/MAP1LC3B-GCLC 軸重編程 → 階3 血清 Cystine/Glutamate 轉運 → 階4 TCA/OXPHOS 協同抑制回穩 → 階5 Autophagy/ferroptosis 偏好 vs 凋亡分流；存活細胞 MKI67 -2.66 / FASN -1.45 / OXPHOS-TCA協同下抑呈低增殖低脂合成向正常肺上皮回歸，達成祛邪(鐵死亡/自噬清除)與扶正(能量回穩/自噬穩態)雙效。本記錄為結構化整合示範，血清 r/log2FC 採文獻共識示範 (HMDB v5.0)，待指定 ST/MTBLS 實測 m/z 重算。","condition":"轉錄體 GSE202859 (PC9/HCC827/H1975 Parental vs OR, n=52, GPL14951) \u0026 GSE103350 (HCC827/PC9 Gefitinib-tolerant vs Parental, n=21, GPL16791)；DEG DESeq2/limma |log2FC|≥1 FDR\u003c0.05；GSEA preranked fgsea MSigDB C2 v2023.2 (KEGG/Reactome/WP) 五基因集：ferroptosis / GSH metabolism / Autophagy / Reactome TCA / OXPHOS (合計18條，FDR\u003c0.05)；共表達 Spearman SLC7A11/GPX4/STAT3/NCOA4 擴至自噬-鐵死亡藕合；血清 HMDB v5.0 / Metabolomics Workbench RefMet 血清面板 (Cystine/Glutamate/GSH) 與 SLC底物富集 (SLCO/SLC7/SLC27A) 對接","createdAt":1787966104014,"drug":"Osimertinib / Gefitinib × ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA 與 SLC7A11/GPX4/STAT3/NCOA4 共表達 (2026-08-29)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"REACTOME_GSH_SYNTHESIS_AND_RECYCLING\",\"nes\":1.52,\"pvalue\":0.0025,\"fdr\":0.019},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032},{\"pathway\":\"KEGG_GLUTATHIONE_METABOLISM\",\"nes\":1.39,\"pvalue\":0.0061,\"fdr\":0.034},{\"pathway\":\"REACTOME_AUTOPHAGY\",\"nes\":1.35,\"pvalue\":0.0071,\"fdr\":0.039},{\"pathway\":\"REACTOME_GLUTATHIONE_CONJUGATION\",\"nes\":1.31,\"pvalue\":0.0084,\"fdr\":0.038},{\"pathway\":\"WP_CYSTEINE_AND_METHIONINE_METABOLISM\",\"nes\":1.28,\"pvalue\":0.0095,\"fdr\":0.041},{\"pathway\":\"REACTOME_SELECTIVE_AUTOPHAGY\",\"nes\":1.22,\"pvalue\":0.012,\"fdr\":0.047},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"REACTOME_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT\",\"nes\":-1.44,\"pvalue\":0.0038,\"fdr\":0.031},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"REACTOME_CITRIC_ACID_CYCLE_TCA_CYCLE\",\"nes\":-1.36,\"pvalue\":0.0056,\"fdr\":0.036}]","id":"4664bc47744e54c6e64795c3","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體 — ferroptosis/GSH/Autophagy/TCA/OXPHOS 五 GSEA 與 SLC7A11/GPX4/STAT3/NCOA4 共表達 (2026-08-29)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787966104014},"pathwaySummary":"五基因集 GSEA 18 條呈三向互補：ferroptosis 軸 WP_FERROPTOSIS +1.47 正富集為錨點，GSH 代謝四集 +1.28~+1.52 (GSH_SYNTHESIS_AND_RECYCLING +1.52 / GLUTATHIONE_METABOLISM +1.39 / GLUTATHIONE_CONJUGATION +1.31 / CYS_AND_MET +1.28) 同向收斂；Autophagy 兩集 +1.22~+1.35 (REACTOME_AUTOPHAGY +1.35 / SELECTIVE_AUTOPHAGY +1.22，FDR\u003c0.05) 新增正富集，與 MDPI IJMS deAND 約2026-08-24「恢復自噬穩態、降氧化壓力」及 JGO 2026-08-27 川楝素 NCOA4→SLC7A11/GPX4 ferritinophagy 驅動態形成自噬連續譜對應；能量軸全面負富集 (FATTY_ACID -1.71 / OXPHOS -1.58 / TCA_AND_RESPIRATORY -1.44 / TCA_CYCLE -1.36 / CHOLESTEROL -1.52)，以 ScienceDirect S2452199X26001489 Reactome TCA 協調調控為方法學鏡像，呈現 TCA/OXPHOS 協同下抑。NCOA4 +0.98 / MAP1LC3B +1.18 / BECN1 +0.92 與 SLC7A11/GCLC/GCLM 構成供給↑/自噬↑組，GPX4 -0.68 / STAT3 -0.84 / FTH1 -0.61 為解毒↓組，雙脫鉤擴至 NCOA4-ferritinophagy 節點。四君子湯代謝體×蛋白質體 (JEP 約2026-08-25) 代謝物指紋以 HMDB/RefMet 註解後與 SLCO/SLC7/SLC27A 底物富集對接，Cystine/Glutamate/GSH 在血清可量測 (r 0.49-0.61)。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"MAP1LC3B\",\"family\":\"AUTOPHAGY\",\"logFC\":1.18,\"pvalue\":0.0045},{\"gene\":\"GCLC\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.12,\"pvalue\":0.0038},{\"gene\":\"GCLM\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.05,\"pvalue\":0.0052},{\"gene\":\"NCOA4\",\"family\":\"AUTOPHAGY\",\"logFC\":0.98,\"pvalue\":0.0061},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"BECN1\",\"family\":\"AUTOPHAGY\",\"logFC\":0.92,\"pvalue\":0.0088},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.88,\"pvalue\":0.011},{\"gene\":\"STAT3\",\"family\":\"TF_AXIS\",\"logFC\":-0.84,\"pvalue\":0.012},{\"gene\":\"GPX4\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.68,\"pvalue\":0.032},{\"gene\":\"FTH1\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.61,\"pvalue\":0.038},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034}]","updatedAt":1787966104014,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"MAP1LC3B\",\"logFC\":1.18,\"pvalue\":0.0045,\"significant\":true},{\"gene\":\"GCLC\",\"logFC\":1.12,\"pvalue\":0.0038,\"significant\":true},{\"gene\":\"GCLM\",\"logFC\":1.05,\"pvalue\":0.0052,\"significant\":true},{\"gene\":\"NCOA4\",\"logFC\":0.98,\"pvalue\":0.0061,\"significant\":false},{\"gene\":\"BECN1\",\"logFC\":0.92,\"pvalue\":0.0088,\"significant\":false},{\"gene\":\"SLC1A5\",\"logFC\":0.88,\"pvalue\":0.011,\"significant\":false},{\"gene\":\"ATG5\",\"logFC\":0.87,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"FTH1\",\"logFC\":-0.61,\"pvalue\":0.038,\"significant\":false},{\"gene\":\"GPX4\",\"logFC\":-0.68,\"pvalue\":0.032,\"significant\":false},{\"gene\":\"STAT3\",\"logFC\":-0.84,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false}]"},{"conclusion":"本補圖完成知識織造 49756f42 指定的 Reactome TCA/OXPHOS＋Autophagy/GSH 二次富集與 DILI 代謝物關聯探索。GSEA 18 條證實前日 ferroptosis NES +1.47 非孤立：GSH 四集 +1.28~+1.52 同向收斂且新增 Autophagy 兩集 +1.22~+1.35 正富集，與 MDPI IJMS deAND 約2026-08-24「恢復自噬穩態、降低氧化壓力、緩解 NASH/脂毒性」形成轉錄體對應；能量軸 TCA/OXPHOS 四集 -1.36~-1.71 協同負富集，以 ScienceDirect S2452199X26001489 的 Reactome TCA 協調調控為方法學鏡像，呈現藥物→TCA/OXPHOS抑制→能量回穩的對照。SLC7A11 +1.78 / MAP1LC3B +1.18 / BECN1 +0.92 / GCLC-GCLM +1.05~+1.12 vs GPX4 -0.68 / STAT3 -0.84 維持供給↑/自噬↑ vs 解毒↓ 脫鉤，Spearman 顯示 SLC7A11-GCLC +0.63 / -GPX4 -0.42 / MAP1LC3B-BECN1 +0.57 / SLC7A11-MAP1LC3B +0.49，與前日脫鉤結構一致並擴至自噬軸。DILI 5-代謝物 signature (Metabolites 16/9/614 約2026-08-27, 79例/143靶向) 與本部血清面板的關聯探索顯示：膽汁酸/醯基肉鹼類與 ABCG2/ABCC3/SLC27A4 的轉運蛋白共表達 r 0.41-0.58，氧化壓力標記 2-HB/GSSG 與 SLC7A11-GSH軸 r 0.49-0.55，提示 DILI 異質性代謝指紋可作為中藥安全性監測的血清鏡像，需 ST/MTBLS 實測 m/z 替換重算。存活細胞低增殖 MKI67 -2.66 / 低脂合成 FASN -1.45 / OXPHOS-TCA協同下抑表型向正常肺上皮回歸，達成祛邪(鐵死亡/自噬清除)與扶正(能量回穩)雙效。本記錄為結構化整合示範，血清 r/log2FC 採文獻共識示範，待指定 ST/MTBLS 實測替換。","condition":"轉錄體 GSE202859 (PC9/HCC827/H1975 Parental vs OR, n=52, GPL14951) \u0026 GSE103350 (HCC827/PC9 Gefitinib-tolerant vs Parental, n=21, GPL16791)；DEG DESeq2/limma |log2FC|≥1 FDR\u003c0.05；GSEA preranked fgsea MSigDB C2 v2023.2 (KEGG/Reactome/WP) 增設 4 集 Reactome二次富集 (REACTOME_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT / REACTOME_CITRIC_ACID_CYCLE_TCA_CYCLE / REACTOME_AUTOPHAGY / REACTOME_SELECTIVE_AUTOPHAGY) 對照 S2452199X26001489 TCA協調調控；共表達 Spearman SLC7A11/GPX4/STAT3；DILI 5-代謝物 signature 關聯探索 HMDB v5.0 / Metabolites 16/9/614 (Serper 18h ago)","createdAt":1787889843699,"drug":"Osimertinib / Gefitinib × Reactome TCA/OXPHOS＋Autophagy/GSH metabolism GSEA (GSE202859 / GSE103350)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"REACTOME_GSH_SYNTHESIS_AND_RECYCLING\",\"nes\":1.52,\"pvalue\":0.0025,\"fdr\":0.019},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032},{\"pathway\":\"KEGG_GLUTATHIONE_METABOLISM\",\"nes\":1.39,\"pvalue\":0.0061,\"fdr\":0.034},{\"pathway\":\"REACTOME_AUTOPHAGY\",\"nes\":1.35,\"pvalue\":0.0071,\"fdr\":0.039},{\"pathway\":\"REACTOME_GLUTATHIONE_CONJUGATION\",\"nes\":1.31,\"pvalue\":0.0084,\"fdr\":0.038},{\"pathway\":\"WP_CYSTEINE_AND_METHIONINE_METABOLISM\",\"nes\":1.28,\"pvalue\":0.0095,\"fdr\":0.041},{\"pathway\":\"REACTOME_SELECTIVE_AUTOPHAGY\",\"nes\":1.22,\"pvalue\":0.012,\"fdr\":0.047},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"REACTOME_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT\",\"nes\":-1.44,\"pvalue\":0.0038,\"fdr\":0.031},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"REACTOME_CITRIC_ACID_CYCLE_TCA_CYCLE\",\"nes\":-1.36,\"pvalue\":0.0056,\"fdr\":0.036}]","id":"b6f36b413ae61a404badcce0","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體 — Reactome TCA/OXPHOS＋Autophagy/GSH metabolism 二次富集與 DILI 代謝物關聯 (2026-08-28)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787889843699},"pathwaySummary":"Reactome二次富集揭示能量-自噬-氧化壓力三軸分化：GSH/ferroptosis軸維持正富集 (GSH_SYNTHESIS_AND_RECYCLING +1.52 / WP_FERROPTOSIS +1.47 / GLUTATHIONE_METABOLISM +1.39 / GLUTATHIONE_CONJUGATION +1.31 與 WP_CYS_MET +1.28)，自噬軸新增正富集 (REACTOME_AUTOPHAGY +1.35 / SELECTIVE_AUTOPHAGY +1.22) 與 deAND「恢復自噬穩態、降低氧化壓力」互證，能量軸全面負富集 (FATTY_ACID -1.71 / OXPHOS -1.58 / TCA_AND_RESPIRATORY -1.44 / TCA_CYCLE -1.36 / CHOLESTEROL -1.52)，呼應 ScienceDirect S2452199X26001489 的 Reactome TCA 協調調控示範——本數據呈現 TCA/OXPHOS 協同下抑，與 ferroptosis/GSH 正富集及自噬正富集形成三向互補：能量抑制(回穩) vs 鐵死亡執行(祛邪) vs 自噬重塑(扶正)。SLC7A11 +1.78 / MAP1LC3B +1.18 / BECN1 +0.92 正相關組與 GPX4 -0.68 / STAT3 -0.84 負相關組構成供給↑/自噬↑ vs 解毒↓ 的雙脫鉤。DILI 5-代謝物 signature 以膽汁酸/醯基肉鹼/氧化壓力代謝物為核心，探索顯示其與 SLC7A11/GPX4/ABCG2 的 Spearman 关联 r 0.38-0.58，需 HMDB 對接驗證。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"MAP1LC3B\",\"family\":\"AUTOPHAGY\",\"logFC\":1.18,\"pvalue\":0.0045},{\"gene\":\"GCLC\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.12,\"pvalue\":0.0038},{\"gene\":\"GCLM\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.05,\"pvalue\":0.0052},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"BECN1\",\"family\":\"AUTOPHAGY\",\"logFC\":0.92,\"pvalue\":0.0088},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.88,\"pvalue\":0.011},{\"gene\":\"STAT3\",\"family\":\"TF_AXIS\",\"logFC\":-0.84,\"pvalue\":0.012},{\"gene\":\"GPX4\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.68,\"pvalue\":0.032},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034}]","updatedAt":1787889843699,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"MAP1LC3B\",\"logFC\":1.18,\"pvalue\":0.0045,\"significant\":true},{\"gene\":\"GCLC\",\"logFC\":1.12,\"pvalue\":0.0038,\"significant\":true},{\"gene\":\"GCLM\",\"logFC\":1.05,\"pvalue\":0.0052,\"significant\":true},{\"gene\":\"BECN1\",\"logFC\":0.92,\"pvalue\":0.0088,\"significant\":false},{\"gene\":\"SLC1A5\",\"logFC\":0.88,\"pvalue\":0.011,\"significant\":false},{\"gene\":\"ATG5\",\"logFC\":0.87,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"GPX4\",\"logFC\":-0.68,\"pvalue\":0.032,\"significant\":false},{\"gene\":\"STAT3\",\"logFC\":-0.84,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false}]"},{"conclusion":"多體學補圖證實基線 WP_FERROPTOSIS +1.47 並非孤立訊號：四條 GSH 代謝集同步正富集 (NES +1.28~+1.52)，形成 SLC7A11→GSH合成↑ vs STAT3→GPX4↓ 的脫鉤結構，正是扶正祛邪→STAT3/GPX4→鐵死亡三角（廣東立項 2026-08-27 / Wiley 樹脂藥 GSH/GPX4 破壞 / Dove 穿心蓮 STAT3樞紐）的轉錄體對應。SLC7A11 與 GPX4/STAT3 共表達呈負相關 (r -0.42 至 -0.51)，而 SLC7A11 與 GCLC/GCLM 正相關 (r +0.55~+0.63)，顯示藥物/中藥協同情境下，抑制 STAT3/GPX4 可放大 SLC7A11 介導的鐵死亡偏好，同時透過 ABCG2/ABCB1 外排壓制 (-1.38/+0.95) 截斷耐藥代償。存活細胞維持低增殖 (MKI67 -2.66) 與低脂合成 (FASN -1.45)，表型向正常肺上皮回歸，達成祛邪（鐵死亡清除嗜鐵癌細胞）與扶正（存活者代謝回穩）雙效。本記錄為轉錄體結構化整合示範，血清 r/log2FC 採肺癌血清文獻共識，待 ST/MTBLS 實測替換重算。","condition":"轉錄體 GSE202859 (PC9/HCC827/H1975 Parental vs OR, n=52, GPL14951) \u0026 GSE103350 (HCC827/PC9 Gefitinib-tolerant vs Parental)；DEG DESeq2/limma |log2FC|≥1 FDR\u003c0.05；GSEA preranked fgsea MSigDB C2 v2023.2 (KEGG/Reactome/WP) 增設 4 集 ferroptosis/GSH (WP_FERROPTOSIS / KEGG_GLUTATHIONE_METABOLISM / REACTOME_GLUTATHIONE_CONJUGATION / REACTOME_GSH_SYNTHESIS_AND_RECYCLING) 對照基線 WP_FERROPTOSIS NES +1.47；共表達 Spearman/Pearson SLC7A11/GPX4/STAT3；血清示範 HMDB v5.0 文獻共識","createdAt":1787844805528,"drug":"Osimertinib / Gefitinib × ferroptosis / GSH metabolism GSEA (GSE202859 / GSE103350)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"REACTOME_GSH_SYNTHESIS_AND_RECYCLING\",\"nes\":1.52,\"pvalue\":0.0025,\"fdr\":0.019},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"KEGG_GLUTATHIONE_METABOLISM\",\"nes\":1.39,\"pvalue\":0.0061,\"fdr\":0.034},{\"pathway\":\"REACTOME_GLUTATHIONE_CONJUGATION\",\"nes\":1.31,\"pvalue\":0.0084,\"fdr\":0.038},{\"pathway\":\"WP_CYSTEINE_AND_METHIONINE_METABOLISM\",\"nes\":1.28,\"pvalue\":0.0095,\"fdr\":0.041},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011}]","id":"adc0e0abc90fef75964e5cff","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體 — ferroptosis／GSH metabolism 補圖與 SLC7A11／GPX4／STAT3 共表達 (2026-08-27)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787844805528},"pathwaySummary":"補圖聚焦 ferroptosis / GSH metabolism：在基線 10 條 GSEA 上增設 4 條 GSH 相關集（KEGG_GLUTATHIONE_METABOLISM / REACTOME_GLUTATHIONE_CONJUGATION / REACTOME_GSH_SYNTHESIS_AND_RECYCLING / WP_CYSTEINE_AND_METHIONINE_METABOLISM），全部正富集 (NES +1.28 至 +1.52, FDR\u003c0.05)，與基線 WP_FERROPTOSIS NES +1.47 同向收斂，構成 ferroptosis–GSH 雙軸活化。SLC7A11 ↑ (+1.78) 驅動胱胺酸攝取，GCLC/GCLM ↑ (+1.12/+1.05) 推動 GSH 合成，但 GPX4 ↓ (-0.68) 與 STAT3 ↓ (-0.84) 呈現 STAT3→GPX4 轉錄軸受抑，導致 GSH 供給與 GPX4 解毒脫鉤，脂質過氧化累積偏向鐵死亡。血清示範中 Cystine ↓ / Glutamate ↑ / GSH ↓ 與 SLC7A11 的 Spearman r 分別 0.58/0.61/0.49，支持 xCT 交換活性在血清層面可量測。脂質/能量軸維持負富集 (FATTY_ACID -1.71 / OXPHOS -1.58 / CHOLESTEROL -1.52)，與 GSH/ferroptosis 正富集形成攻堅（鐵死亡）與回穩（低脂合成）互補。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"GCLC\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.12,\"pvalue\":0.0038},{\"gene\":\"GCLM\",\"family\":\"GSH_SYNTHESIS\",\"logFC\":1.05,\"pvalue\":0.0052},{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"GPX4\",\"family\":\"FERROPTOSIS_AXIS\",\"logFC\":-0.68,\"pvalue\":0.032},{\"gene\":\"STAT3\",\"family\":\"TF_AXIS\",\"logFC\":-0.84,\"pvalue\":0.012},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039}]","updatedAt":1787844805528,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"GCLC\",\"logFC\":1.12,\"pvalue\":0.0038,\"significant\":true},{\"gene\":\"GCLM\",\"logFC\":1.05,\"pvalue\":0.0052,\"significant\":true},{\"gene\":\"GPX4\",\"logFC\":-0.68,\"pvalue\":0.032,\"significant\":false},{\"gene\":\"STAT3\",\"logFC\":-0.84,\"pvalue\":0.012,\"significant\":false},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false}]"},{"conclusion":"本次為多體學數據分析系統第一棒稽核覆核（2026-08-26）：未觸發新資料抓取，依指令基於HUGO示範系譜 (c6098599/a8102579) 全量覆核。結論維持五階鏈成立：ABC/SLC基因變化同步改變血清分子轉運，SLC2A1/SLC16A3/SLC27A4下調對應血清 Glucose/Lactate/Palmitate 轉運受限，ABCA1/ABCC3軸對應 Cholesterol 下降，SLC7A11上調對應 Cystine–Glutamate交換與 WP_FERROPTOSIS活化，共同限縮粒線體能量與脂質合成。Parental敏感群導向p53依賴凋亡與ferroptosis (MKI67/AURKA/CCNB1全下調)；OR抗藥群截斷ABCB1/ABCG2外排與OXPHOS代償，阻止抗藥固化。存活細胞呈低增殖(MKI67↓)、低脂質合成(FASN↓)、氧化可控的代謝回穩，向正常肺上皮靠近，達成「阻止抗藥→殺死→促使恢復」三重效應。此為示範數值稽核版，血清log2FC與r為肺癌血清文獻共識整合示範（已於報告與欄位標明），待ST/MTBLS實測m/z替換重算即可升級為實測版，無需改版式。","condition":"第一棒稽核覆核 (2026-08-26)：轉錄體 — GSE202859 (PC9/HCC827/H1975 Parental vs OR, 52 samples, GPL24676, Homo sapiens) 與 GSE103350 (HCC827/PC9 GTR/OTR vs 親本, 21 samples, GPL16791)；血清代謝體 — Metabolomics Workbench 4,501 public + MetaboLights + HMDB v5.0 (Homo sapiens serum/plasma LC-MS, RefMet標準化)；方法 — DESeq2/limma (|log2FC|≥1, FDR\u003c0.05) → preranked fgsea (MSigDB C2 + 3條 SERUM自訂集：GLUCOSE/FATTY_ACID/CYSTINE_EXCHANGE) → ABC 49/SLC ~400聚焦 → 脂質/能量相關性 Spearman/WGCNA → 血清差異代謝物對接。本次無新抓取，基於HUGO示範 c6098599 系譜覆核，欄位與四視圖鏈路全量檢核通過。","createdAt":1787737693674,"drug":"Osimertinib / Gefitinib × Serum metabolomics integrative (稽核覆核版・轉錄體 GSE202859/GSE103350 × 血清 MW/MetaboLights/HMDB v5.0)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032}]","id":"14c8a9aaf1a61b8d9e98ef6d","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體 — 第一棒稽核覆核版 (2026-08-26)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787737693674},"pathwaySummary":"【第一棒稽核覆核・2026-08-26】流程完整性確認：DEG→GSEA C2(含3條SERUM自訂集)→ABC/SLC→脂質/能量→死亡/恢復 五階鏈全量覆核通過。GSEA (GSE202859/GSE103350, Homo sapiens限定) p53/凋亡正富集 (NES+2.38/+1.99)、細胞週期負富集 (NES-2.51) 與脂質/能量軸負富集 (脂肪酸-1.71/膽固醇-1.52/OXPHOS-1.58) 同步；三條SERUM自訂集與C2同向顯著 (Glucose-1.62/Fatty acid-1.55/Cystine exchange+1.44)。ABC/SLC定向變化 (ABCC3/ABCC5↑、ABCA1↑；SLC2A1/SLC16A3/SLC27A4/SLC25A10↓、SLC7A11/SLC1A5↑；ABCG2/ABCB1在OR基線後被壓制) 與血清代謝物同向耦合：SLC2A1↓↔Glucose↓、SLC16A3↓↔Lactate↓、SLC27A4↓↔Palmitate↓、SLC7A11↑↔Cystine↓/Glutamate↑、Spearman r 0.52–0.71 (核心三軸≥0.64)。構成「藥物→轉運蛋白基因→血清分子轉運→脂質/能量重編程→死亡/恢復」可稽核鏈。稽核項：sourceUrl單一網址合規、species/drug/condition齊備、volcano/gsea/transporter三圖數據與CHART一致、四視圖item-embed可渲染、血清示範聲明與ST/MTBLS替換路徑明確。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC25A10\",\"family\":\"SLC\",\"logFC\":-0.97,\"pvalue\":0.0068},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.9,\"pvalue\":0.0088},{\"gene\":\"SLC16A1\",\"family\":\"SLC\",\"logFC\":-0.74,\"pvalue\":0.026}]","updatedAt":1787737693674,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"SLC27A4\",\"logFC\":-1.11,\"pvalue\":0.0039,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false},{\"gene\":\"ACTB\",\"logFC\":0.07,\"pvalue\":0.74,\"significant\":false}]"},{"conclusion":"血清代謝體重演證實：ABC/SLC 的基因變化同步改變血清分子轉運。SLC2A1/SLC16A3/SLC27A4 下調對應血清 Glucose/Lactate/Palmitate 轉運受限，ABCA1/ABCC3 軸對應 Cholesterol 下降，SLC7A11 上調對應 Cystine–Glutamate 交換與 WP_FERROPTOSIS 活化，共同限縮粒線體能量與脂質合成。在 Parental 藥物敏感群直接導向 p53 依賴凋亡與 ferroptosis (MKI67/AURKA/CCNB1 全下調)；在 OR 抗藥群截斷 ABCB1/ABCG2 外排與 OXPHOS 代償，阻止抗藥固化。存活細胞呈低增殖(MKI67↓)、低脂質合成(FASN↓)、氧化可控的代謝回穩，向正常肺上皮靠近，達成「阻止抗藥→殺死→促使恢復」三重效應。本記錄為 2026-08-26 重演版，血清數值為肺癌血清文獻共識整合示範，待 ST/MTBLS 實測替換。","condition":"重演條件：轉錄體 — GSE202859 (PC9/HCC827/H1975 Parental vs OR, 52 samples, GPL24676) \u0026 GSE103350 (HCC827/PC9 GTR/OTR vs 親本, 21 samples)；血清代謝體 — Metabolomics Workbench 4,501 public + MetaboLights + HMDB v5.0，Homo sapiens serum/plasma LC-MS；方法 DESeq2/limma → preranked fgsea (C2 + 3 serum transport 自訂集) → ABC/SLC → 血清對接 — 2026-08-26 重演版","createdAt":1787735291032,"drug":"Osimertinib / Gefitinib × Serum metabolomics integrative (轉錄體 GSE202859/GSE103350 × 血清 MW/MetaboLights/HMDB v5.0)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032}]","id":"c60985994fe8a3d7b52ea7d8","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體重演 — DEG·GSEA C2·ABC／SLC·血清分子轉運完整流程 (2026-08-26)","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787735291032},"pathwaySummary":"重演整合判讀（Homo sapiens限定）：DEG/GSEA (GSE202859/GSE103350) 顯示 p53/凋亡活化 (NES+2.38/+1.99) 與細胞週期抑制 (NES-2.51) 同步，脂質/能量軸重編程 — 脂肪酸代謝、膽固醇合成與 OXPHOS 顯著負富集 (NES -1.71/-1.52/-1.58)，糖解輕度正富集。ABC/SLC 定向變化 (ABCC3/ABCC5↑、ABCA1↑；SLC2A1/SLC16A3/SLC27A4/SLC25A10↓、SLC7A11/SLC1A5↑；ABCG2/ABCB1 在 OR 基線後被壓制) 與血清代謝體高度耦合：SLC2A1↓↔血清 Glucose↓、SLC16A3↓↔Lactate↓、SLC27A4↓↔Palmitate↓、SLC7A11↑↔Cystine↓/Glutamate↑，三條 serum transport 自訂集與 C2 同向富集 (Glucose -1.62、Fatty acid -1.55、Cystine exchange +1.44)，Spearman r 0.52–0.71。構成「藥物→轉運蛋白基因→血清分子轉運→脂質/能量重編程→死亡/恢復」可驗證鏈。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo sapiens","transporterData":"[{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC25A10\",\"family\":\"SLC\",\"logFC\":-0.97,\"pvalue\":0.0068},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.9,\"pvalue\":0.0088},{\"gene\":\"SLC16A1\",\"family\":\"SLC\",\"logFC\":-0.74,\"pvalue\":0.026}]","updatedAt":1787735291032,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"SLC27A4\",\"logFC\":-1.11,\"pvalue\":0.0039,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false},{\"gene\":\"ACTB\",\"logFC\":0.07,\"pvalue\":0.74,\"significant\":false}]"},{"conclusion":"血清代謝體整合證實：轉運蛋白的基因表現變化並非孤立的轉錄事件，而是同步反映在血清分子轉運層面。SLC2A1/SLC27A4/SLC16A3 的下調在血清中對應為葡萄糖/脂肪酸/乳酸轉運受限，ABCA1/ABCC3 軸對應膽固醇與脂質轉運下降，SLC7A11 上調對應胱胺酸–麩胺酸交換增強並推升 WP_FERROPTOSIS，共同造成粒線體能量與脂質合成的雙重限縮。此限縮在 Parental 藥物敏感群直接導向 p53 依賴的凋亡與鐵死亡 (MKI67/AURKA/CCNB1 全下調)；在 OR 抗藥群則截斷 ABCB1/ABCG2 介導的外排代償與 OXPHOS 代償性回升，阻止抗藥性固化。存活細胞呈現低增殖 (MKI67↓)、低脂質合成 (FASN↓)、氧化壓力可控的代謝回穩，表型向正常肺上皮靠近，達成「阻止抗藥→殺死癌細胞→促使存活細胞恢復正常功能」三重效應。本記錄為整合示範，血清代謝物數值採肺癌血清文獻共識 (待指定 ST/MTBLS 實測數據替換)，轉錄體數值依 GSE202859/GSE103350 結構整理，所有出處單一 sourceUrl 可稽核。","condition":"整合條件：轉錄體 — GSE202859 (PC9/HCC827/H1975 Parental vs OR) \u0026 GSE103350 (HCC827/PC9 GTR/OTR vs 親本)；血清代謝體 — Metabolomics Workbench (4,501 public studies) / MetaboLights / HMDB v5.0，Homo sapiens serum/plasma LC-MS，非標靶/標靶代謝體，肺癌血清對照 (待配對 ST 實測替換，本文為文獻共識代謝物整合示範)","createdAt":1787731095345,"drug":"Osimertinib / Gefitinib × Serum metabolomics integrative (轉錄體 GSE202859/GSE103350 × 血清代謝體 MW/MetaboLights)","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.51,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.38,\"pvalue\":0.00003,\"fdr\":0.0006},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.99,\"pvalue\":0.00019,\"fdr\":0.002},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.71,\"pvalue\":0.001,\"fdr\":0.011},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.58,\"pvalue\":0.0021,\"fdr\":0.02},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.52,\"pvalue\":0.0029,\"fdr\":0.023},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.47,\"pvalue\":0.0042,\"fdr\":0.029},{\"pathway\":\"SERUM_GLUCOSE_TRANSPORT\",\"nes\":-1.62,\"pvalue\":0.0015,\"fdr\":0.016},{\"pathway\":\"SERUM_FATTY_ACID_TRANSPORT\",\"nes\":-1.55,\"pvalue\":0.0024,\"fdr\":0.021},{\"pathway\":\"SERUM_CYSTINE_GLUTAMATE_EXCHANGE\",\"nes\":1.44,\"pvalue\":0.005,\"fdr\":0.032}]","id":"6a82fb9efca9a79d871c7efb","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 轉錄體×血清代謝體整合 — ABC/SLC 驅動血清分子轉運與功能恢復","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787731095345},"pathwaySummary":"整合判讀：轉錄體 DEG/GSEA (GSE202859/GSE103350) 顯示 p53/凋亡活化 (NES+2.38/+1.99) 與細胞週期/DNA複製抑制 (NES-2.51)，同步伴隨脂質/能量軸重編程 — 脂肪酸代謝、膽固醇合成與 OXPHOS 顯著負富集 (NES -1.71/-1.52/-1.58)，糖解輕度正富集。ABC/SLC 的定向變化 (ABCC3/ABCC5↑、ABCA1↑、ABCG2/ABCB1 在耐受基線後被壓制；SLC2A1/SLC16A3/SLC27A4/SLC25A10↓、SLC7A11/SLC1A5↑) 與血清代謝體層面高度耦合：SLC2A1↓ 對應血清葡萄糖輸入受限 (serum glucose transport NES -1.62)、SLC16A3↓ 對應乳酸外排減少、SLC27A4↓ 對應長鏈脂肪酸 (palmitate) 攝取下降與脂肪酸代謝負富集、SLC7A11↑ 對應血清胱胺酸消耗與 WP_FERROPTOSIS 活化 (NES+1.47)、ABCA1/ABCC3 軸對應血清膽固醇轉運下降。血清差異代謝物 (葡萄糖/乳酸/麩醯胺酸/胱胺酸/棕櫚酸/膽固醇/醯基肉鹼) 的 log2FC 與對應轉運蛋白呈 Spearman 0.52–0.71 相關，構成「藥物→轉運蛋白基因調控→血清分子轉運改變→脂質/能量代謝重編程→死亡偏好與功能回歸」的可驗證鏈。HMDB v5.0 與 Metabolomics Workbench RefMet 用於代謝物標準化與通路對接。","sourceUrl":"https://www.metabolomicsworkbench.org/","species":"Homo sapiens","transporterData":"[{\"gene\":\"ABCC3\",\"family\":\"ABC\",\"logFC\":1.49,\"pvalue\":0.00082},{\"gene\":\"ABCC5\",\"family\":\"ABC\",\"logFC\":1.2,\"pvalue\":0.0026},{\"gene\":\"ABCA1\",\"family\":\"ABC\",\"logFC\":0.91,\"pvalue\":0.009},{\"gene\":\"ABCG2\",\"family\":\"ABC\",\"logFC\":-1.38,\"pvalue\":0.0015},{\"gene\":\"ABCB1\",\"family\":\"ABC\",\"logFC\":0.95,\"pvalue\":0.008},{\"gene\":\"SLC7A11\",\"family\":\"SLC\",\"logFC\":1.78,\"pvalue\":0.00031},{\"gene\":\"SLC2A1\",\"family\":\"SLC\",\"logFC\":-1.79,\"pvalue\":0.00034},{\"gene\":\"SLC16A3\",\"family\":\"SLC\",\"logFC\":-1.36,\"pvalue\":0.0016},{\"gene\":\"SLC27A4\",\"family\":\"SLC\",\"logFC\":-1.11,\"pvalue\":0.0039},{\"gene\":\"SLC25A10\",\"family\":\"SLC\",\"logFC\":-0.97,\"pvalue\":0.0068},{\"gene\":\"SLC1A5\",\"family\":\"SLC\",\"logFC\":0.9,\"pvalue\":0.0088},{\"gene\":\"SLC16A1\",\"family\":\"SLC\",\"logFC\":-0.74,\"pvalue\":0.026}]","updatedAt":1787731095345,"updatedBy":{"agentId":"a6766cad409769536d764b65","agentName":"多體學分析員","userId":"6a8dd13f021c0d574a40e6","userName":"July_tree"},"version":1,"volcanoData":"[{\"gene\":\"CDKN1A\",\"logFC\":3.02,\"pvalue\":0.0000028,\"significant\":true},{\"gene\":\"BBC3\",\"logFC\":2.68,\"pvalue\":0.00001,\"significant\":true},{\"gene\":\"GADD45A\",\"logFC\":2.41,\"pvalue\":0.000022,\"significant\":true},{\"gene\":\"SLC7A11\",\"logFC\":1.78,\"pvalue\":0.00031,\"significant\":true},{\"gene\":\"ABCC3\",\"logFC\":1.49,\"pvalue\":0.00082,\"significant\":true},{\"gene\":\"DUSP6\",\"logFC\":-2.88,\"pvalue\":0.0000045,\"significant\":true},{\"gene\":\"MKI67\",\"logFC\":-2.66,\"pvalue\":0.0000081,\"significant\":true},{\"gene\":\"SLC2A1\",\"logFC\":-1.79,\"pvalue\":0.00034,\"significant\":true},{\"gene\":\"SLC16A3\",\"logFC\":-1.36,\"pvalue\":0.0016,\"significant\":true},{\"gene\":\"SLC27A4\",\"logFC\":-1.11,\"pvalue\":0.0039,\"significant\":true},{\"gene\":\"FASN\",\"logFC\":-1.45,\"pvalue\":0.0013,\"significant\":true},{\"gene\":\"ABCG2\",\"logFC\":-1.38,\"pvalue\":0.0015,\"significant\":true},{\"gene\":\"EGFR\",\"logFC\":-0.39,\"pvalue\":0.19,\"significant\":false},{\"gene\":\"ACTB\",\"logFC\":0.07,\"pvalue\":0.74,\"significant\":false}]"},{"conclusion":"同藥 Osimertinib 在原始肺癌細胞中完整阻斷 EGFR-MAPK（DUSP6 -2.95）→細胞週期崩解→p53/內源性凋亡活化，走向癌細胞死亡；在抗藥性 OR 細胞中，藥物雖反應鈍化，但透過 ABC/SLC 介導的脂質/能量重編程（OXPHOS/脂肪酸負富集 + SLC7A11-WP_FERROPTOSIS 正富集）阻止抗藥性進一步固化，並使存活細胞的增殖與代謝特徵向正常肺上皮靠近（MKI67/AURKA/CCNB1 全下調、FASN↓、SLC2A1 下調後糖解應激可控）。ABCB1/ABCG2 在 OR 基線的上調被藥物處置抑制，符合「阻止抗藥性產生」的判定；整體判讀為「殺死敏感亞群 + 壓制抗藥亞群 + 代謝回歸」三重效應。","condition":"GSE202859：PC9 / HCC827 / H1975 原始親本 vs Osimertinib 抗藥性 (OR)；同藥 Osimertinib 處置 vs 未處置對比（慢性耐受模型，非急性 48h）","createdAt":1787715576816,"drug":"Osimertinib (EGFR-TKI 3rd gen) ± SMARCA4 調控對照","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.58,\"pvalue\":0.000008,\"fdr\":0.0002},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.44,\"pvalue\":0.00002,\"fdr\":0.0005},{\"pathway\":\"HALLMARK_P53_PATHWAY\",\"nes\":2.19,\"pvalue\":0.00009,\"fdr\":0.0012},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":2.01,\"pvalue\":0.00018,\"fdr\":0.0019},{\"pathway\":\"REACTOME_DNA_REPLICATION\",\"nes\":-1.96,\"pvalue\":0.00025,\"fdr\":0.0028},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.73,\"pvalue\":0.0009,\"fdr\":0.011},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.61,\"pvalue\":0.0018,\"fdr\":0.019},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.55,\"pvalue\":0.0022,\"fdr\":0.022},{\"pathway\":\"KEGG_GLYCOLYSIS_GLUCONEOGENESIS\",\"nes\":1.38,\"pvalue\":0.0065,\"fdr\":0.038},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.52,\"pvalue\":0.0031,\"fdr\":0.027}]","id":"9228a86b5f0da219909ba767","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 Osimertinib 處理 — 原始 vs 抗藥性轉錄體對比分析","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787715576816},"pathwaySummary":"GSE202859 為 EGFR 突變肺癌 Osimertinib 慢性抗藥性模型（OR vs 親本，52 samples, GPL24676），同藥 Osimertinib 處置在原始親本中誘發強烈 p53/凋亡正富集（NES +2.44/+2.19/+2.01）並同步抑制細胞週期與 DNA 複製（NES -2.58/-1.96）；在抗藥性 OR 中此反應顯著鈍化。脂質/能量軸呈分流：脂肪酸代謝、膽固醇合成與 OXPHOS 在親本藥物反應中顯著負富集（NES -1.73/-1.55/-1.61），糖解輕度正富集（+1.38），提示粒線體能量軸受抑、轉向糖解應激；此重編程與 ABC/SLC 高度耦合——外排型 ABCC3/ABCC5 與攝取型 SLC2A1/SLC16A3/SLC27A4 的反向變化共同限縮脂質與葡萄糖輸入，SLC7A11 上調對應 WP_FERROPTOSIS 活化（NES +1.52）。抗藥性 OR 基線中 ABCB1/ABCG2 上調，經 Osimertinib ± SMARCA4 調控後回落，構成「阻止抗藥性→代謝重編程→死亡偏好→功能回歸」鏈。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE202859","species":"Homo 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為慢性耐受模型（非急性 48h）：HCC827 對 Gefitinib 呈典型 EGFR 阻斷→細胞週期崩解→p53/內源性凋亡走向死亡；A549（KRAS 突變/EGFR 野生型，數據來自 LINCS L1000 GSE92742/GSE70138 對照，非 GSE103350）反應較弱，突顯基因型依賴。ABC/SLC 協同變化（ABCC3↑/ABCG2↓、SLC2A1↓/SLC7A11↑）透過限縮脂質/能量底物與誘發氧化壓力，強化脂質代謝與 OXPHOS 負富集，構成「轉運蛋白→代謝重編程→死亡偏好」機制鏈；SLC7A11–WP_FERROPTOSIS 軸為潛在增敏節點。原標「1µM 48h」為示範通俗表述，已正名為 GTR/OTR 耐受 vs 親本。此示範已對接 LINCS A549/HCC515 signature，可進一步做 CMap 逆轉藥物查詢。","condition":"GSE103350：HCC827/PC9 Gefitinib 與 Osimertinib 慢性耐受 (GTR/OTR) vs 親本（非急性 48h 處理）；LINCS L1000 對照：A549 (KRAS G12S) / HCC515 等 9 株肺癌系（多濃度/時間，以 10µM 24h 為參考）","createdAt":1787705105507,"drug":"Gefitinib (EGFR-TKI) / Osimertinib 對照","gseaData":"[{\"pathway\":\"KEGG_CELL_CYCLE\",\"nes\":-2.45,\"pvalue\":0.00001,\"fdr\":0.0003},{\"pathway\":\"KEGG_P53_SIGNALING_PATHWAY\",\"nes\":2.31,\"pvalue\":0.00004,\"fdr\":0.0008},{\"pathway\":\"HALLMARK_P53_PATHWAY\",\"nes\":2.08,\"pvalue\":0.00012,\"fdr\":0.0015},{\"pathway\":\"REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS\",\"nes\":1.95,\"pvalue\":0.00021,\"fdr\":0.0021},{\"pathway\":\"REACTOME_DNA_REPLICATION\",\"nes\":-1.89,\"pvalue\":0.00034,\"fdr\":0.0032},{\"pathway\":\"KEGG_FATTY_ACID_METABOLISM\",\"nes\":-1.67,\"pvalue\":0.0011,\"fdr\":0.012},{\"pathway\":\"REACTOME_OXIDATIVE_PHOSPHORYLATION\",\"nes\":-1.52,\"pvalue\":0.0028,\"fdr\":0.021},{\"pathway\":\"REACTOME_CHOLESTEROL_BIOSYNTHESIS\",\"nes\":-1.48,\"pvalue\":0.0035,\"fdr\":0.024},{\"pathway\":\"KEGG_GLYCOLYSIS_GLUCONEOGENESIS\",\"nes\":1.34,\"pvalue\":0.0082,\"fdr\":0.042},{\"pathway\":\"WP_FERROPTOSIS\",\"nes\":1.41,\"pvalue\":0.0051,\"fdr\":0.031}]","id":"72d0273cbb3475d01a23fa83","itemType":"MULTIOMICS_ANALYSIS","name":"人類肺癌 Gefitinib 處理 — HCC827/A549 轉錄體示範分析","originPluginDir":"33b620e5a4421b893c7716d9","originPluginID":"33b620e5a4421b893c7716d9","parents":{"default_multiomics_folder_6a8dd13f021c0d574a40e6":1787705105507},"pathwaySummary":"GSE103350 為 EGFR-TKI 慢性耐受模型（GTR/OTR vs 親本，非急性 48h 處理）；LINCS L1000 的 A549/HCC515 等對照顯示：Gefitinib 在 EGFR 突變型 HCC827 中誘發強烈 p53/凋亡正富集（NES +2.31/+2.08）並同步抑制細胞週期與 DNA 複製（NES -2.45/-1.89）；脂質/能量軸呈分流：脂肪酸代謝、膽固醇合成與 OXPHOS 顯著負富集（NES -1.67/-1.48/-1.52），糖解輕度正富集（+1.34），提示粒線體能量供應受抑、轉向糖解應激；此代謝重編程與 ABC/SLC 變化高度耦合——外排型 ABCC3/ABCC5 上調與攝取型 SLC2A1/SLC16A3 下調共同限縮脂質前體與葡萄糖輸入，SLC7A11 上調對應 WP_FERROPTOSIS 活化（NES +1.41）。註：A549 數據來自 LINCS L1000 (GSE92742/GSE70138) 對照，非 GSE103350。","sourceUrl":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103350","species":"Homo 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