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基于 CytoHubba 的 11 种拓扑分析方法鉴定与胃癌相关的生物标志物。

Identifying of biomarkers associated with gastric cancer based on 11 topological analysis methods of CytoHubba.

机构信息

School of Mathematics and Statistics, Southwest University, Chongqing, 400715, China.

Department of Pediatric Respiration, Chongqing Ninth People's Hospital, Chongqing, 400700, China.

出版信息

Sci Rep. 2021 Jan 14;11(1):1331. doi: 10.1038/s41598-020-79235-9.

Abstract

Gastric cancer (GC) is one of the most common types of malignancy. Its potential molecular mechanism has not been clarified. In this study, we aimed to explore potential biomarkers and prognosis-related hub genes associated with GC. The gene chip dataset GSE79973 was downloaded from the GEO datasets and limma package was used to identify the differentially expressed genes (DEGs). A total of 1269 up-regulated and 330 down-regulated genes were identified. The protein-protein interactions (PPI) network of DEGs was constructed by STRING V11 database, and 11 hub genes were selected through intersection of 11 topological analysis methods of CytoHubba in Cytoscape plug-in. All the 11 selected hub genes were found in the module with the highest score from PPI network of all DEGs by the molecular complex detection (MCODE) clustering algorithm. In order to explore the role of the 11 hub genes, we performed GO function and KEGG pathway analysis for them and found that the genes were enriched in a variety of functions and pathways among which cellular senescence, cell cycle, viral carcinogenesis and p53 signaling pathway were the most associated with GC. Kaplan-Meier analysis revealed that 10 out of the 11 hub genes were related to the overall survival of GC patients. Further, seven of the 11 selected hub genes were verified significantly correlated with GC by uni- or multivariable Cox model and LASSO regression analysis including C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1. C3, CDK1, FN1, CCNB1, CDC20, BUB1B and MAD2L1 may serve as potential prognostic biomarkers and therapeutic targets for GC.

摘要

胃癌(GC)是最常见的恶性肿瘤类型之一。其潜在的分子机制尚未阐明。在本研究中,我们旨在探索与 GC 相关的潜在生物标志物和预后相关的枢纽基因。从 GEO 数据集下载基因芯片数据集 GSE79973,并使用 limma 包识别差异表达基因(DEGs)。共鉴定出 1269 个上调基因和 330 个下调基因。通过 STRING V11 数据库构建 DEGs 的蛋白质-蛋白质相互作用(PPI)网络,通过 Cytoscape 插件中的 CytoHubba 的 11 种拓扑分析方法的交集选择 11 个枢纽基因。通过分子复合物检测(MCODE)聚类算法,所有 11 个选定的枢纽基因都位于所有 DEGs 的 PPI 网络中得分最高的模块中。为了探讨 11 个枢纽基因的作用,我们对它们进行了 GO 功能和 KEGG 通路分析,发现这些基因富集在多种功能和通路中,其中细胞衰老、细胞周期、病毒致癌和 p53 信号通路与 GC 相关性最强。Kaplan-Meier 分析显示,11 个枢纽基因中有 10 个与 GC 患者的总生存率相关。进一步的,通过单变量或多变量 Cox 模型和 LASSO 回归分析验证,11 个选定的枢纽基因中的 7 个与 GC 显著相关,包括 C3、CDK1、FN1、CCNB1、CDC20、BUB1B 和 MAD2L1。C3、CDK1、FN1、CCNB1、CDC20、BUB1B 和 MAD2L1 可能作为 GC 的潜在预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1663/7809423/cd4cf2a87752/41598_2020_79235_Fig1_HTML.jpg

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