细胞分裂周期蛋白6拷贝数变异与肺腺癌患者预后关系的研究

Study on the relationship between copy number variation of cell division cycle 6 gene with prognosis of patients with lung adenocarcinoma

目的探讨细胞分裂周期蛋白6(CDC6)基因在肺腺癌组织中的拷贝数变异(CNV)对肺腺癌预后的影响。方法从癌症基因组图谱(TCGA)数据库中获取肺腺癌患者的转录谱(mRNA)数据、CNV数据及临床资料,使用基因表达谱动态分析(GEPIA)数据库对CDC6基因在肺腺癌组织中的表达情况,及其与CDC6基因CNV和肺腺癌患者预后的关系进行分析。筛选CDC6基因的共表达基因,并进行基因组百科全书(KEGG)通路分析及基因本体(GO)功能富集分析。结果肺腺癌患者肿瘤组织中CDC6基因CNV与CDC6mRNA的表达量呈正相关(P﹤0.01)。CDC6低表达组肺腺癌患者的生存结局明显优于CDC6高表达组患者(P﹤0.01)。KEGG通路分析结果显示:CDC6基因的共表达基因富集在DNA复制、错配修复、核苷酸切除修复等修复相关通路。GO功能富集分析结果显示:在生物学过程层面,CDC6基因的共表达基因主要参与了DNA链的延伸、核酸切除修复、蛋白质去甲酰化、转录偶联切除修复、WNT信号通路、平面细胞极性通路、核因子-κB诱导激酶(NIK)/核因子-κB(NF-κB)信号通路;在细胞构成层面,CDC6基因的共表达基因参与了T复合物、透明带受体复合物、驱动蛋白复合体、DNA复制因子C复合物的形成;在分子功能层面,CDC6基因的共表达基因参与四链体DNA结合。结论CDC6基因CNV可以对肺腺癌组织中CDC6基因的表达进行调控,CDC6基因及其共表达基因可对肺腺癌的DNA复制、修复过程和肿瘤相关信号通路进行调控并可能以此为基础影响肺腺癌的发展进程。CDC6基因高表达肺腺癌患者的预后不良,其可能成为预测肺腺癌临床预后的有效生物标志物。

Objective To investigate the effect of copy number variation (CNV) of cell division cycle 6 (CDC6) gene on the prognosis of lung adenocarcinoma.Method The transcriptional profile (mRNA) data,CNV data and clinical data of lung adenocarcinoma patients were downloaded from The Cancer Genome Atlas (TCGA) database.Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the gene expression of CDC6 gene in lung adenocarcinoma issues and its relationship with CNV of CDC6 gene and prognosis of lung adenocarcinoma patients.The co-expression genes of CDC6 gene were screened,and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene ontology (GO) function enrichment analysis were carried out.Result There was a positive correlation between CNV of CDC6 gene and CDC6 mRNA expression in lung adenocarcinoma tissues (P<0.01).The survival outcome of lung adenocarcinoma patients with low expression of CDC6 was significantly better than that of patients with high expression of CDC6 (P<0.01).KEGG pathway analysis showed that the co-expression genes of CDC6 gene were enriched in DNA replication,mismatch repair,nucleotide excision repair and other repair-related pathways.GO functional enrichment analysis showed that the co-expression genes of CDC6 gene were mainly involved in DNA strand extension,nucleic acid excision repair,protein de-formylation,transcriptional coupling excision repair,WNT signaling pathway,planar cell polarity pathway,nuclear factor of kappa-B binducing kinase (NIK)/nuclear factor of kappa-B (NF-κB) signaling pathway at the level of biological processes.CDC6 gene co-expression genes were involved in T complex,zona pellucida receptor complex,driving protein complex and DNA replication factor C complex at cell composition level.At the molecular level,the co-expression genes of CDC6 gene were involved in four-stranded DNA binding.Conclusion In lung adenocarcinoma, CNV of CDC6 gene has a regulatory effect on its expression,and CDC6 gene and its co-expression genes regulate DNA replication,repair process and cancer- related signaling pathways.It may influence the development.The prognosis of patients with lung adenocarcinoma with high expression of CDC6 gene is poor,which may be an effective biomarker for predicting the clinical prognosis of lung adenocarcinoma.