Abstract:

Objective　To investigate the correlation between gastric cancer gene sets and clinical characteristics and to identify the candidate biomarkers analyzing the key functional modules of stomach cancer by the weighted gene co-expression network analysis (WGCNA). Methods　The study was from January to April 2023. The gene expression profile of GSE65801 was screened from the Comprehensive Gene Expression Omnibus (GEO). WGCNA was used to construct the gene co-expression network of gastric cancer and to identify the co-expression modules. Function (GO) and pathway (KEGG) enrichment analyses and protein interaction (PPI) analysis were performed. The prognostic genes were screened out by survival analysis. Results　Twelve co-expression modules were obtained by the WGCNA, and the modules with the most significant differences were selected for subsequent studies. These genes were mainly predominantly enriched in mucoglycan metabolism, vascular development, epithelial cell proliferation, regulation of cell response to growth factor stimulation, regulation of cell growth, cell adhesion, and other functions, as well as key signaling pathways, such as PI3K-Akt, MAPK, and Ras. Five prognostic related genes were screened out by the prognostic analysis, including VCAN, SERPINE1, HGF, IGFBP7, and FSTL3. Conclusion　Some gastric cancer related modules and prognostic genes are identified by WGCNA, which provides a crucial theoretical basis for further research on the molecular mechanism underlying the occurrence and development of gastric cancer as well as targeted therapy.

Key words:

Stomach cancer, Weighted gene co-expression network analysis, Survival analysis, Protein interaction

摘要：

目的　运用加权基因共表达网络分析法（weighted gene co-expression network analysis，WGCNA）分析胃癌关键功能模块，研究胃癌基因集与临床特征的相关性，并鉴定候选生物标志物。方法　研究时间2023年1月至4月。在基因表达综合数据库（Gene Expression Omnibus，GEO）中筛选出GSE65801的基因表达谱，运用WGCNA构建胃癌的基因共表达网络并识别共表达模块，分别进行功能（GO）、通路（KEGG）富集分析和蛋白质相互作用（PPI）分析，并通过生存分析筛选出预后相关基因。结果　通过WGCNA得到12个共表达模块，选取其中差异最显著的模块进行后续研究，这些基因主要富集到糖胺聚糖代谢、血管发育、上皮细胞增殖、调节细胞对生长因子刺激的反应、调节细胞生长、细胞粘附等功能上，以及PI3K-Akt、MAPK、Ras等关键信号通路上，最终通过预后分析筛选出5个预后相关基因：VCAN、SERPINE1、HGF、IGFBP7、FSTL3。结论　通过WGCNA识别出一些与胃癌相关的模块和预后相关基因，为进一步研究胃癌的发生发展的分子机制以及靶向治疗提供重要的理论依据。

关键词:

胃癌, 加权基因共表达网络分析法, 生存分析, 蛋白质相互作用