应用生物信息学方法筛选食管鳞癌的关键基因

The key genes in esophageal squamous cell carcinoma screened by bioinformatics

目的筛选食管鳞癌的关键基因,为肿瘤的发病机制研究提供新的思路。方法检索GEO数据库中食管鳞癌基因表达芯片,分析差异表达基因并获得共同差异基因;利用在线数据库DAVID进行GO和KEGG通路富集分析;通过String数据库和Cytoscape软件分析获取链接度最高的10个关键基因,并在TCGA数据库中验证。结果共筛选出204个差异表达基因。GO分析显示其生物学过程富集在细胞分裂、细胞器断裂和细胞周期等163个条目中;细胞学组分富集在细胞外、细胞质和细胞器腔内等48个条目中;分子功能富集在调控肽酶活性、与细胞外基质结合等46个条目中。KEGG通路富集在局部黏附、p53信号通路、错配修复等12个条目中。筛选出10个链接度最高的Hub基因,且通过TCGA数据库验证其全部在食管鳞癌组织中高表达(P <0.01)。结论 CDK1、CCNA2、RFC4、CCNB1、TOP2A、AURKA、CDC6、BUB1、BUB1B、PLK1是食管鳞癌的关键基因,可能是食管鳞癌的生物标志和治疗靶点。

Objective To provide new ideas for the study of tumor pathogenesis by screening the key genes of esophageal squamous cell carcinoma(ESCC). Methods The gene expression chips of ESCC were retrieved in GEO database. The differential expression genes were analyzed for obtaining common differential genes. GO and KEGG pathway enrichment analysis were performed in DAVID online database. The 10 key genes with the highest link were obtained by String database and Cytoscape software, and verified in the TCGA database. Results A total of 204 differentially expressed genes were screened. GO analysis showed that the biological process was enriched in 163 items,such as cell division, organelle fission, cell cycle, etc. Cytological components were enriched in 48 entries including extracellular, cytoplasmic and organelle lumen. Molecular function enrichment in 46 entries, such as regulating peptidase activity, binding to extracellular matrix, etc. KEGG pathways were enriched in 12 entries, including local adhesion, p53 signaling pathways, mismatch repair, etc. The 10 highest-linked Hub genes were verified to be highly expressed in ESCC by TCGA databases(P < 0.01). Conclusion CDK1, CCNA2, RFC4, CCNB1, TOP2 A, AURKA, CDC6,BUB1, BUB1 B and PLK1 are the key genes of ESSC, and may be biomarkers and therapeutic targets in ESCC.