肝癌潜在关键基因的鉴定及共表达网络的构建

Identification of Potential Key Genes in Liver Cancer and Construction of Co-Expression Networks

摘要: 肝癌(HCC)的发生发展与慢性炎症、肝纤维化及代谢调控异常密切相关。为系统评估IGF2R基因在肝癌中的表达特征及其潜在作用，本研究基于GEO数据库GSE36376数据集，对193例正常肝组织与240例HCC样本开展差异表达分析和WGCNA加权基因共表达网络分析。主要发现如下：1) IGF2R基因在HCC组织中显著上调，提示其可能参与肿瘤发生。2) WGCNA结果显示，在软阈值为11的条件下共识别4个共表达模块，其中MEturquoise模块与肝癌表型呈最强正相关(r = 0.88, p = 1e−142)，其模块基因中有较高比例的模块成员度(MM)和基因显著性(GS)均大于0.5，富集于多条肿瘤相关信号通路。3) 在进一步采用更严格阈值(MM > 0.8且GS > 0.8)筛选核心基因(hub genes)时，IGF2R位于模块的高影响力区域，显示其可能作为驱动肝癌进展的关键基因。本研究系统揭示了IGF2R在肝癌相关共表达网络中的重要地位，可为肝纤维化及肝癌的预测性生物标志物筛选和潜在治疗靶点开发提供新的思路。

Abstract: The development and progression of hepatocellular carcinoma (HCC) are closely associated with chronic inflammation, liver fibrosis, and dysregulated metabolic processes. To systematically evaluate the expression characteristics and potential role of IGF2R gene in HCC, this study utilized the GSE36376 dataset from the GEO database and performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) on 193 normal liver tissues and 240 HCC samples. The main findings are as follows: 1) IGF2R was significantly upregulated in HCC tissues, suggesting its potential involvement in tumor initiation. 2) WGCNA identified four co-expression modules under a soft-threshold power of 11, among which the MEturquoise module exhibited the strongest positive correlation with the HCC phenotype (r = 0.88, p = 1e−142). A large proportion of genes within this module showed high module membership (MM) and gene significance (GS) values greater than 0.5, and these genes were enriched in multiple cancer-related signaling pathways. 3) Using more stringent criteria (MM > 0.8 and GS > 0.8) to screen for hub genes, IGF2R was found to be located in a high-influence region within the module, indicating that it may serve as a key driver gene in HCC progression. Collectively, this study highlights the pivotal role of IGF2R within HCC-associated gene co-expression networks and provides new insights for identifying predictive biomarkers and potential therapeutic targets for liver fibrosis and HCC.