Yuan Yihang, Chen Ji, Wang Jue, Xu Ming, Zhang Yunpeng, Sun Peng, Liang Leilei
Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2020 Apr 30;10:638. doi: 10.3389/fonc.2020.00638. eCollection 2020.
Colorectal cancer (CRC) is the third leading cause of death in the world. However, the key roles of most molecules in CRC remain unclear. This study aimed to identify key modules and hub genes associated with the progression of CRC. The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R. by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified, which were associated with clinical traits. Next, we screened hub genes related to the progression of CRC authenticated by The Cancer Genome Atlas (TCGA) and Oncomine databases. Three hub genes (HCLS1, EVI2B, and CD48) were identified, and survival analysis was further performed. Moreover, the results of qPCR and immunohistochemistry staining revealed that HCLS1, EVI2B, and CD48 are tumor suppressor genes. Further, the functional study verified that over-expression of HCLS1, EVI2B, and CD48 can reduce the proliferation, migration, and invasion ability of CRC cells and significantly suppress CRC tumor growth . In summary, we identified three hub genes that were associated with the progression of CRC that can be applied in treatment.
结直肠癌(CRC)是全球第三大死因。然而,大多数分子在CRC中的关键作用仍不清楚。本研究旨在识别与CRC进展相关的关键模块和枢纽基因。CRC患者的数据从基因表达综合数据库(GEO)中获取,并通过加权基因共表达网络分析(WGCNA)、基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析在R中进行评估。通过WGCNA,鉴定出了几个调节CRC肿瘤发生机制的枢纽基因,这些基因与临床特征相关。接下来,我们筛选了经癌症基因组图谱(TCGA)和Oncomine数据库验证的与CRC进展相关的枢纽基因。鉴定出三个枢纽基因(HCLS1、EVI2B和CD48),并进一步进行了生存分析。此外,qPCR和免疫组织化学染色结果显示,HCLS1、EVI2B和CD48是肿瘤抑制基因。进一步的功能研究证实,HCLS1、EVI2B和CD48的过表达可降低CRC细胞的增殖、迁移和侵袭能力,并显著抑制CRC肿瘤生长。总之,我们鉴定出了三个与CRC进展相关的枢纽基因,可用于治疗。