胶原蛋白作为胃癌潜在生物标志物的生物信息学分析

doi:10.3969/j.issn.1004-616x.2021.06.002

摘要/Abstract

摘要： 目的： 应用生物信息学方法探讨胃癌的潜在生物标志物。方法： 检索与“Gastric cancer”相关的数据集，使用R语言和韦恩图分析胃癌中的差异表达基因（DEGs）；使用DAVID软件对DEGs进行功能注释；利用STRING数据库构建蛋白相互作用网络并确定核心基因；Oncomine数据库分析核心基因在胃癌中的表达模式；最后，利用Kaplan-Meier数据库分析核心基因的预后价值。结果： NCBI筛选获得3个与胃癌相关的数据集，得到了110个DEGs。功能富集分析显示，DEGs主要富集在细胞外基质受体相互作用的功能和途径中。其中一组基因在胃癌组织中显著上调，并以COL1A1、COL1A2、COL2A1、COL12A1、COL6A3、COL10A1等为重要节点构成蛋白质-蛋白质相互作用网络。利用miRNA-mRNA分析发现hsa-miR-29a-3p、hsa-miR-29b-3p和hsa-miR-29c-3p可以同时调控COL1A1、COL1A2、COL6A3和COL2A1，且均属于hsa-miR-29家族成员。进一步分析核心蛋白在胃癌中的表达情况，发现collagen家族成员中COL1A1、COL1A2、COL12A1、COL6A3、COL10A1等在胃癌组织中均较正常胃组织表达上调（P<0.05）。生存分析显示COL1A1、COL1A2、COL12A1、COL6A3、COL2A1和COL10A1高表达患者较低表达患者预后差（P<0.05）。结论： 本研究发现胶原蛋白在胃癌中表达明显上调，并与胃癌患者的预后密切相关，可能是胃癌患者潜在的生物标志物。

关键词: 胃癌, 生物信息学, 差异表达基因, 胶原蛋白

Abstract: OBJECTIVE: To identify potential biomarkers for gastric cancers (GC) through bioinformatics methods. METHODS: Gene Expression Omnibus (GEO) were retrieved from GC-related datasets,followed by R software and Venn analyses for differentially expressed genes (DEGs) in GC. DAVID software was used to distinguish DEGs' functional annotation. Expression patterns of DEGs were analyzed by Oncomine and their prognostic values were examined by Kaplan-Meier plotter. RESULTS: Three GC-related GEO datasets were found and downloaded from NCBI. After integrating them,110 DEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a protein-protein interaction network as important nodes,including COL1A1,COL1A2,COL2A1,COL12A1,COL6A3,and COL10A1. Based on the miRNA-mRNA analysis,hsa-miR-29a-3p,hsa-miR-29b-3p,and hsa-miR-29c-3p which belonged to the hsa-miR-29 family,has the potential for regulation of COL1A1,COL1A2,COL6A3 and COL2A1. Compared with normal gastric tissues,the expression of COL1A1,COL1A2,COL12A1,COL6A3 and COL10A1 were significantly up-regulated in GC (P<0.05). From survival analyses,the GC patients with high expression of COL1A1,COL1A2,COL12A1,COL6A3,COL2A1 and COL10A1 had poorer prognosis than the other GC patients (P<0.05). CONCLUSION: This study identified that expression of collagen genes was significantly up-regulated in GC tissues and associated with GC patients' survival. Their oncogenic roles and prognostic values in GC indicate that collagens could serve as potential therapeutic targets of GC.

Key words: gastric cancer, bioinformatics, differentially expressed genes, collagen

中图分类号:

R735.2

杨婵君, 陈雯恬, 刘静. 胶原蛋白作为胃癌潜在生物标志物的生物信息学分析[J]. 癌变·畸变·突变, 2021, 33(6): 410-419.

YANG Chanjun, CHEN Wentian, LIU Jing. Bioinformatics analysis of gastric cancer datasets regarding collagen as a possible biomarker[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 410-419.

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