南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (10): 1422-1431.doi: 10.12122/j.issn.1673-4254.2020.10.07

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SAC复合体相关基因TTK和MAD2L1基因在肺腺癌中过表达：基于大数据的生物信息学分析

刘 铸，郭泽钦，龙利丽，张艳培，卢钰雯，吴德华，董忠谊   

  • 出版日期:2020-10-20 发布日期:2020-10-20

Spindle assembly checkpoint complex-related genes TTK and MAD2L1 are overexpressed in lung adenocarcinoma: a big data and bioinformatics analysis

  • Online:2020-10-20 Published:2020-10-20

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摘要： 目的 通过大数据筛选与肺腺癌预后相关的关键基因并探讨其临床价值和潜在机制。方法 基于基因表达综合数据库（GEO）中获得的GSE18842，GSE27262以及GSE33532基因表达谱进行数据分析；生物信息学方法筛选肿瘤组织和正常肺组织的差异表达基因，对其进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）富集分析后进行蛋白质-蛋白质相互作用网络（PPI）、模组、表达差异和预后分析和筛选。35例非小细胞肺癌标本和35例配对的癌旁正常组织，共70例组织标本分为肿瘤组和正常组对MAD2L1和TTK的表达进行了免疫组化验证。结果 共有256个基因的表达谱数据有统计学差异（P<0.05），包括66个上调基因，190个下调基因。进行功能分析后筛选出 32 个上调基因。32个基因中的29与肺腺癌预后显著相关。相较与正常肺组织，所有29个基因均在肺腺癌组织中高表达并主要富集在细胞周期通路。其中7个关键基因与纺锤体组装检查点（SAC）复合体紧密相关，负责调控细胞G2/M期行为。我们选择了SAC相关基因TTK和MAD2L1，在肺腺癌患者组织标本中观察到了TTK和MAD2L1相较与癌旁正常肺组织的过表达。结论 以TTK和MAD2L1为代表的7个SAC复合体相关基因在肺腺癌患者中存在过表达，且其过表达与预后相关。

关键词: 生物信息学分析, 基因芯片, 非小细胞肺癌, 肺腺癌, 差异表达基因

Abstract: Objective To screen the key genes related to the prognosis of lung adenocarcinoma through big data analysis and explore their clinical value and potential mechanism. Methods We analyzed GSE18842, GSE27262, and GSE33532 gene expression profile data obtained from the Gene Expression Omnibus (GEO). Bioinformatics methods were used to screen the differentially expressed genes in lung adenocarcinoma tissues and KEGG and GO enrichment analysis was performed, followed by PPI interaction network analysis, module analysis, differential expression analysis, and prognosis analysis. The expressions of MAD2L1 and TTK by immunohistochemistry were verified in 35 non-small cell lung cancer specimens and paired adjacent tissues. Results We identified a total of 256 genes that showed significant differential expressions in lung adenocarcinoma, including 66 up-regulated and 190 down-regulated genes. Thirty-two up-regulated core genes were screened by functional analysis, and among them 29 were shown to significantly correlate with a poor prognosis of patients with lung adenocarcinoma. All the 29 genes were highly expressed in lung adenocarcinoma tissues compared with normal lung tissues and were mainly enriched in cell cycle pathways. Seven of these key genes were closely related to the spindle assembly checkpoint (SAC) complex and responsible for regulating cell behavior in G2/M phase. We selected SAC-related proteins TTK and MAD2L1 to test their expressions in clinical tumor samples, and detected their overexpression in lung adenocarcinoma tissues as compared with the adjacent tissues. Conclusion Seven SAC complex-related genes, including TTK and MAD2L1, are overexpressed in lung adenocarcinoma tissues with close correlation with the prognosis of the patients.

Key words: bioinformatical analysis, microarray, non-small cell lung cancer, lung adenocarcinomas, differentially expressed genes