基于组学数据对离子通道基因突变致癌机制研究

Research on the Oncogenic Mechanisms of Ion Channel Gene Mutations Based on Multi-Omics Data

摘要: 本研究基于TCGA数据库中多种消化道肿瘤(包括肝细胞癌、胃腺癌、结肠癌、胰腺癌及食管癌)的组学数据，旨在探究离子通道基因突变在肿瘤发生发展中的致癌机制及其对患者预后的影响。研究首先通过严格的质控标准筛选样本，随后利用单因素Cox比例风险回归模型筛选出与患者总生存期显著相关的15个离子通道基因。研究进一步通过共突变分析揭示了这些基因及其家族成员间存在协同与互斥的突变模式，表明它们可能通过形成复杂的调控网络发挥作用。功能富集分析(GO与KEGG)显示，这些基因主要参与离子跨膜转运、膜电位调控等核心生物学过程。最后，通过构建蛋白质–蛋白质相互作用(PPI)网络，研究鉴定出CACNB1、KCNB2、TRPC6等核心枢纽基因。研究结论认为，离子通道基因突变通过破坏细胞离子稳态等机制，在消化道肿瘤的进展中发挥重要作用，并为预后评估和潜在的治疗靶点提供了新的线索。

Abstract: This study utilized multi-omics data from The Cancer Genome Atlas (TCGA) across several gastrointestinal malignancies—including hepatocellular carcinoma, gastric adenocarcinoma, colorectal cancer, pancreatic cancer, and esophageal cancer—to investigate the oncogenic mechanisms of ion channel gene mutations in tumor development and progression, as well as their impact on patient prognosis. First, samples were screened using stringent quality control criteria. Subsequently, univariate Cox proportional hazards regression analysis was applied to identify 15 ion channel genes significantly associated with overall survival. Co-mutation analysis further revealed synergistic and mutually exclusive mutation patterns among these genes and their family members, suggesting that they may function through complex regulatory networks. Functional enrichment analyses (GO and KEGG) indicated that these genes are primarily involved in key biological processes such as transmembrane ion transport and membrane potential regulation. Finally, by constructing a protein-protein interaction (PPI) network, the study identified CACNB1, KCNB2, and TRPC6 as central hub genes. Overall, the findings suggest that mutations in ion channel genes contribute to the progression of gastrointestinal cancers by disrupting cellular ion homeostasis, and they provide new insights for prognostic evaluation and potential therapeutic targets.