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基于WGCNA方法的肝癌预后研究

Prognostic genes of hepatocellular carcinoma revealed by gene co-expression network analysis

中文摘要英文摘要

【目的】肝细胞癌是一种侵袭性恶性肿瘤,目前,确定肝癌复发风险高的患者是有挑战性的,需要额外的疗法。本文应用加权基因共表达网络分析(WGCNA)和Cox比例风险回归分析,开发了一种基因表达模型,用于鉴定可作为HCC预后标志物的基因。【方法】本文通过加权基因共表达网络对训练集的差异表达基因进行聚类分析得到四个模块,再借助逐步Cox风险比例对模块的特征向量进行回归分析,选出与生存密切相关的模块,并进行功能富集和通路富集分析,了解其聚类原因。最后建立单因素Cox风险比例回归模型筛选出模块中与生存期密切相关的基因,以评估基因表达水平与未复发率之间的关系,使用测试集进行验证,绘制Kaplan-Meier曲线,采用对数秩检验进行检验,并将基因标记的分组与临床信息等作为协变量,进行多因素Cox回归分析。【结果】我们从turquoise模块中得到45个与无复发生存期密切相关的基因,该模块中基因与细胞的代谢过程密切相关,不仅BCLC分期等变量与肝癌的预后相关,这些基因标记也可作为肝癌的预后的一个指标。本研究可以提高对肝癌分子发病机制及预后研究的认识。

【Objective】Hepatocellularcarcinoma (HCC) is an aggressive malignancy. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. By applying weighted gene co-expression network analysis (WGCNA) and Cox proportional hazards regression analysis, we developed a gene-expression model for identifying genes that may serve as markers for HCC prognosis.【Methods】In this paper, the weighted gene co-expression network is used to cluster the differentially expressed genes in the training set to obtain four modules.Then using multivariate Cox proportional hazards regression analysis with stepwise selection, we select the modules that were significantly associated with patient survival time and perform functional enrichment and pathway enrichment analysis to understand the reasons for clustering. Finally,univariate cox proportional hazards regression analysis model was established to screen out the closely related genes in the module to evaluate the relationship between gene expression level and non-recurrence rate. The test set is used for verification. Then draft Kaplan-Meier curves. The rank test was performed, and the gene marker grouping and clinical information were used as covariates for multivariate cox regression analysis.【Results】We obtained 45 genes from the turquoise module that are closely related to recurrence-free survival. The genes in this module are closely related to the metabolic processes of cells.Not only variables such as BCLC staging are associated with the prognosis of hepatocellular carcinoma, but these gene markers can also be used as an indicator of the prognosis of hepatocellular carcinoma. The findings of this study can improve the understanding of the molecular pathogenesis and prognosis of hepatocellular carcinoma.

李鑫、张娟

肿瘤学基础医学医学研究方法

肝细胞癌差异表达基因加权基因共表达网络ox风险比例回归

Hepatocellular carcinomaDifferentially expressed genesWeighted gene co-expression network analysisCox proportional hazards regression model

李鑫,张娟.基于WGCNA方法的肝癌预后研究[EB/OL].(2018-10-23)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/201810-55.点此复制

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