Additional file 3 of Insights into gemcitabine resistance in pancreatic cancer: association with metabolic reprogramming and TP53 pathogenicity in patient derived xenografts

Supplementary Material 3: Additional File 3: Table S1. Differentially expressed genes at baseline in gemcitabine-sensitive vs. gemcitabine-resistant models with unadjusted p < 0.001. Table S2. Significant differences in drug-associated changes in gene expression (i.e., deltas post-treatment vs. baseline) between sensitive and resistant models. Table S3. Significantly enriched gene sets between gemcitabine sensitive and resistant PDAC models at baseline. Table S4. Significantly enriched gene sets for genes with different drug-induced expression profiles between gemcitabine sensitive and resistant PDAC models. Table S5. Genes from MSigDB’s cancer hallmark gene sets with drug-induced expression changes significantly correlated with TGI%. Table S6. Significantly enriched pathways in 96 metabolic pathway gene sets. Table S7. Genes in glycolysis and OXPHOS pathways for which gemcitabine-induced expression changes were significantly correlated with TGI%. Table S8. Prevalence of TP53 mutational categories stratified by gemcitabine response status in the Yang and Novartis datasets. Fisher’s exact text p values are indicated for each dataset. Table S9. Significance of the effect of TP53 pathogenic status effect and differences in expression or expression changes on TGI% at 21 days for p53 target genes adjusted for TP53 effect or gene effect.

补充材料3：附加文件3：表S1 吉西他滨敏感模型与吉西他滨耐药模型基线状态下的差异表达基因（未校正P值<0.001）。表S2 敏感与耐药模型间，药物诱导的基因表达变化（即治疗后与基线的表达差值）存在显著差异的基因。表S3 吉西他滨敏感与耐药胰腺导管腺癌（Pancreatic Ductal Adenocarcinoma, PDAC）模型基线状态下显著富集的基因集。表S4 吉西他滨敏感与耐药胰腺导管腺癌（PDAC）模型中，药物诱导表达谱存在差异的基因所对应的显著富集基因集。表S5 来自分子特征数据库（Molecular Signatures Database, MSigDB）癌症特征基因集的基因，其药物诱导的表达变化与肿瘤生长抑制率（Tumor Growth Inhibition, TGI%）显著相关。表S6 96个代谢通路基因集中显著富集的通路。表S7 糖酵解与氧化磷酸化（Oxidative Phosphorylation, OXPHOS）通路中的基因，其吉西他滨诱导的表达变化与肿瘤生长抑制率（TGI%）显著相关。表S8 在Yang数据集与诺华（Novartis）数据集中，按吉西他滨应答状态分层的TP53突变类型占比；各数据集均标注了费希尔精确检验的P值。表S9 针对p53靶基因，校正TP53效应或基因效应后，TP53致病状态的效应、以及表达量或表达变化对21天肿瘤生长抑制率（TGI%）的影响显著性。