Table1_Mitophagy-Related Gene Signature for Prediction Prognosis, Immune Scenery, Mutation, and Chemotherapy Response in Pancreatic Cancer.XLSX

Mitophagy is a conserved cellular process that plays a vital role in maintaining cellular homeostasis by selectively removing dysfunctional mitochondria. Notwithstanding that growing evidence suggests that mitophagy is implicated in pancreatic tumorigenesis, the effect of mitophagy-related genes on pancreatic cancer (PC) prognosis and therapeutic response remains largely unknown. In this study, we sought to construct a mitophagy-related gene signature and assessed its ability to predict the survival, immune activity, mutation status, and chemotherapy response of PC patients. During the screening process, we identified three mitophagy-related genes (PRKN, SRC, VDAC1) from The Cancer Genome Atlas (TCGA) cohort and a 3-gene signature was established. The prognostic model was validated using an International Cancer Genome Consortium (ICGC) cohort and two Gene Expression Omnibus (GEO) cohorts. According to the median risk score, PC patients were divided into high and low-risk groups, and the high-risk group correlated with worse survival in the four cohorts. The risk score was then identified as an independent prognostic predictor, and a predictive nomogram was constructed to guide clinical decision-making. Remarkably, enhanced immunosuppressive levels and higher mutation rates were observed in patients from the high-risk group, which may account for their poor survival. Furthermore, we found that high-risk patients were more sensitive to paclitaxel and erlotinib. In conclusion, a mitophagy-related gene signature is a novel prognostic model that can be used as a predictive indicator and allows prognostic stratification of PC patients.

线粒体自噬（mitophagy）是一种保守的细胞过程，通过选择性清除功能异常的线粒体在维持细胞稳态中发挥至关重要的作用。尽管越来越多的证据表明线粒体自噬与胰腺肿瘤发生密切相关，但线粒体自噬相关基因对胰腺癌（pancreatic cancer, PC）预后及治疗反应的影响仍在很大程度上尚不明确。本研究旨在构建线粒体自噬相关基因特征，并评估其预测胰腺癌患者生存情况、免疫活性、突变状态以及化疗应答的能力。在筛选过程中，我们从癌症基因组图谱（The Cancer Genome Atlas, TCGA）队列中筛选出3个线粒体自噬相关基因（PRKN、SRC、VDAC1），并建立了3基因特征模型。本预后模型通过国际癌症基因组联盟（International Cancer Genome Consortium, ICGC）队列以及两项基因表达综合数据库（Gene Expression Omnibus, GEO）队列进行了验证。根据中位风险评分，胰腺癌患者被分为高风险组与低风险组，在四个队列中，高风险组患者的生存结局均更差。风险评分被证实为独立的预后预测因子，本研究还构建了预测列线图（nomogram）以指导临床决策。值得注意的是，高风险组患者的免疫抑制水平更高、突变率也更高，这或许可以解释其不良生存结局。此外，我们发现高风险患者对紫杉醇（paclitaxel）和厄洛替尼（erlotinib）更为敏感。综上，线粒体自噬相关基因特征是一种新型预后模型，可作为预测指标并实现胰腺癌患者的预后分层。