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HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer

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doi.org2025-03-24 收录
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SUPPLEMENTAL TABLE LIST Table S1. Related to Figure 1: PDCL normalized RNA-seq expression analysis. PDCL consensus clustering using Bailey classification (Squamous Vs Classical) differential gene expression analysis and PDCL class designation (Squamous or Classical). Bulk tumor signature scores of enriched gene expression pathways. Table S2. Related to Figure 1: Untargeted metabolomics and enriched metabolic pathways in Squamous vs Classical PDCLs. Table S3. Related to Figure 1: Seahorse assay: Glycolysis stress test (ECAR values) and Fatty acid Oxidation (Mitochondrial Stress Test, OCR values) in PDCLs. Lactate production and glucose uptake in PDCLs. Table S4. Related to Figure 6 and Figure S1: PDCL point mutations, germline mutations, structural variants and copy number variants. Table S5. Related to Figure 2, Figure 3 and Figure S3: siHNF4A and siGATA6 RNA-seq in Mayo 5289 PDCL. ECAR values after HNF4A knockdown in Classical PDCLs. Table S6: Related to Figure 4 and Figure S4: PDCL siRNA screen, GSK3Bi IC50 (72hr vs 144hr) and GSK3Bi ECAR values. Table S7: Related to Figure 6, Figure 7 and Figure S7: PDCL ATAC-seq analysis. ATAC-seq analysis comparing GSK3Bi initial-responders vs GSK3Bi responders. Survival analysis of PDCLs treated with GSK3Bi + ULKi + PORCNi triple inhibitor treatments. In vivo WNT7A RNAscope analysis.

补充表清单 表S1. 与图1相关:PDCL标准化RNA-seq表达分析。基于Bailey分类(鳞状细胞与经典型)的PDCL共识聚类、差异基因表达分析及PDCL分类(鳞状细胞或经典型)。富含基因表达通路的肿瘤总体特征评分。 表S2. 与图1相关:鳞状细胞与经典型PDCL的未靶向代谢组学和富含代谢通路。 表S3. 与图1相关:Seahorse测试:PDCL中的糖酵解应激测试(ECAR值)和脂肪酸氧化(线粒体应激测试,OCR值)。PDCL中的乳酸产生和葡萄糖摄取。 表S4. 与图6和图S1相关:PDCL点突变、生殖细胞突变、结构变异和拷贝数变异。 表S5. 与图2、图3和图S3相关:Mayo 5289 PDCL中的siHNF4A和siGATA6 RNA-seq。经典型PDCL中HNF4A敲低后的ECAR值。 表S6:与图4和图S4相关:PDCL siRNA筛选、GSK3Bi IC50(72小时与144小时)及GSK3Bi ECAR值。 表S7:与图6、图7和图S7相关:PDCL ATAC-seq分析。比较GSK3Bi初响应者与GSK3Bi响应者的ATAC-seq分析。接受GSK3Bi + ULKi + PORCNi三重抑制剂治疗的PDCL的生存分析。体内WNT7A RNAscope分析。
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