基于加权基因共表达网络分析构建胃癌转移预测模型

背景与目的：通过对高通量功能基因组数据库（Gene Expression Omnibus，GEO）中一组含有转移和非转移性胃癌以及癌旁组织的基因芯片进行加权基因共表达网络分析（weighted gene co-expression network analysis，WGCNA），筛选出与胃癌发生和转移显著相关的分子，为胃癌的治疗和生存期延长的研究提供参考。方法：采用WGCNA方法对19例胃癌患者基因表达进行差异分析；结合临床数据，选取与临床信息高度相关的基因模块构建网络。结果：利用WGCNA我们筛选出了Lightsteelblue模块与胃癌转移明确相关，同时对模块中的基因进一步进行分析，筛选出4个基因：C5AR1、AP3M2、TYMP、ANXA2P1作为核心靶基因。通过表达分析和受试者工作特征（receiver operating characteristic，ROC）曲线分析验证上述基因与胃癌发生、转移明确相关。同时，通过外部ONCOMINE和Kaplan-Meier plot数据库验证上述基因在胃癌中高表达，高表达这些基因的患者有着更差的预后。并利用GSE14210数据集构建基于这些基因的预测患者预后和疾病进展模型。结果提示我们所筛选的4个基因具有成为潜在胃癌转移和治疗生物标志物的可能。结论：鉴定筛选出与胃癌发生和转移相关的4个基因，可为胃癌发生、转移和治疗的研究提供参考。

Construction of a prediction model for metastasis in gastric cancer based on the weighted gene co-expression network analysis

Background and purpose: This study aimed to screen out the bio-markers related to the occurrence and metastasisof gastric cancer. The weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene chips containingmetastatic and non-metastatic gastric cancer and adjacent tissues in Gene Expression Omnibus (GEO) data set. Methods: The geneexpression differences of 19 patients with gastric cancer were analyzed by WGCNA. In combination with clinical data, gene moduleshighly relevant to clinical information were selected to construct the network. Results: Through WGCNA, we screened out theLightsteelblue module that was mostly related to gastric cancer metastasis. Then we further analyzed the genes in the module, andscreened out 4 genes: C5AR1, AP3M2, TYMP, ANXA2P1 as “real” hub genes. Through expression analysis and receiver operatingcharacteristic (ROC) curve analysis, the 4 genes identified were related to the occurrence and metastasis of gastric cancer. Meanwhile,external ONCOMINE and Kaplan-Meier plot databases were used to verify that the above genes were highly expressed in gastriccancer, and patients with high expression of the above genes had a worse prognosis. And the GSE14210 dataset was used to buildthe risk score model to predict the prognosis and progression of disease. These results suggested that the four genes we screenedwere potential bio-markers for gastric cancer metastasis and treatment. Conclusion: In the present study, we screened and identified4 genes related to the occurrence and metastasis of gastric cancer, which could provide evidence for the research on the occurrence,metastasis and treatment of gastric cancer.