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通过生物信息学分析筛选和验证结肠癌中预后不良的关键基因。

Screening and verifying key genes with poor prognosis in colon cancer through bioinformatics analysis.

作者信息

Dong Buyuan, Chai Mengyu, Chen Hao, Feng Qian, Jin Rong, Hu Sunkuan

机构信息

Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Respiratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Transl Cancer Res. 2020 Nov;9(11):6720-6732. doi: 10.21037/tcr-20-2309.

Abstract

BACKGROUND

Colon cancer (CC) is one of the tumors with high morbidity and mortality in the world, and has a trend of younger generation. The molecular level of CC has not been fully elaborated. The purpose of this study is to screen and identify important genes with poor prognosis and their mechanisms at different levels.

METHODS

GSE74602 and GSE10972 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. There were 58 normal tissues and 58 CC tissues. Differentially expressed genes (DEGs) were screened out by using the GEO2R tool and Venn diagram. Then, the DAVID online database was used to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Six hub genes with the highest correlation were screened out after the modular analysis of the protein-protein interaction (PPI) network by using Cytoscape's MCODE plug-in. Finally, the overall survival of key hub genes and potential pathways were verified in GEPIA and UALCAN database.

RESULTS

A total of 78 up-regulated DEGs were enriched in the mitotic nuclear division, cell division, cell proliferation, anaphase-promoting complex-dependent catabolic process and G2/M transition of the mitotic cell cycle. In total, 130 down-regulated DEGs were enriched in muscle contraction, bicarbonate transport, cellular response to zinc ion, negative regulation of growth, negative regulation of leukocyte apoptotic process and one-carbon metabolic process. 2 and were the top six hub genes, mainly enriched in cell cycle pathways. Among them, were enriched in the G2/M phase. GEPIA and UALCAN database confirmed that and had a significant relationship with the poor prognosis of CC patients. Meanwhile, there was a positive correlation between the two.

CONCLUSIONS

Screening out genes with abnormal expression in CC help understand the initiation and progression of CC at the molecular level and explore candidate biomarkers for diagnosis, treatment and prognosis.

摘要

背景

结肠癌(CC)是全球发病率和死亡率较高的肿瘤之一,且有年轻化趋势。CC的分子水平尚未完全阐明。本研究的目的是筛选和鉴定预后不良的重要基因及其在不同水平的机制。

方法

从基因表达综合数据库(GEO)下载GSE74602和GSE10972基因表达谱。有58个正常组织和58个CC组织。使用GEO2R工具和维恩图筛选差异表达基因(DEGs)。然后,利用DAVID在线数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。通过使用Cytoscape的MCODE插件对蛋白质-蛋白质相互作用(PPI)网络进行模块分析后,筛选出相关性最高的6个枢纽基因。最后,在GEPIA和UALCAN数据库中验证关键枢纽基因的总生存期和潜在通路。

结果

共78个上调的DEGs富集于有丝分裂核分裂、细胞分裂、细胞增殖、后期促进复合物依赖性分解代谢过程和有丝分裂细胞周期的G2/M期转换。总共130个下调的DEGs富集于肌肉收缩、碳酸氢盐转运、细胞对锌离子的反应、生长的负调控、白细胞凋亡过程的负调控和一碳代谢过程。2和是前六个枢纽基因,主要富集于细胞周期通路。其中,富集于G2/M期。GEPIA和UALCAN数据库证实和与CC患者的不良预后有显著关系。同时,两者之间呈正相关。

结论

筛选出CC中表达异常的基因有助于从分子水平了解CC的发生和发展,并探索诊断、治疗和预后的候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d8/8797306/564bb5dc17b6/tcr-09-11-6720-f1.jpg

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