Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro
- 1 Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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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 vivo. In summary, we identified three hub genes that were associated with the progression of CRC that can be applied in treatment.
Keywords: clinical validation; co-expression network analysis; colorectal cancer; hub gene; weighted gene.