Identification of key genes in colorectal cancer diagnosis by weighted gene co-expression network analysis

The purpose of this study was using bioinformatics tools to identify biomarkers and molecular factors involved in the diagnosis of colorectal cancer, which are effective for the diagnosis and treatment of the disease. We determined differentially expressed genes (DEGs) related to colorectal cancer (CRC) using the data series retrieved from GEO database. Then the weighted gene co-expression network analysis (WGCNA) was conducted to explore co-expression modules related to CRC diagnosis. Next, the relationship between the integrated modules with clinical features such as the stage of CRC was evaluated. Other downstream analyses were performed on selected module genes. In this study, after performing the WGCNA method, a module named blue module which was more significantly associated with the CRC stage was selected for further evaluation. Afterward, the Protein-protein interaction network through sting software for 154 genes of the blue module was constructed and eight hub genes were identified through the evaluation of constructed network with Cytoscape. Among these eight hub genes, upregulation of MMP9, SERPINH1, COL1A2, COL5A2, COL1A1, SPARC, and COL5A1 in CRC was validated in other microarray and TCGA data. Based on the results of the mRNA-miRNA interaction network, SERPINH1 was found as a target gene of miR-940. Finally, results of the DGIDB database indicated that Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, and Bevacizumab, could be used as a therapeutic agent for targeting the MMP9. Furthermore, Ocriplasmin and Collagenase clostridium histolyticum could target COL1A1, COL1A2, COL5A1, and COL5A2. Taken together, the results of the current study indicated that seven hub genes including COL1A2, COL5A1, COL5A2, SERPINH1, MMP9, SPARC, and COL1A1 which were upregulated in CRC could be used as a diagnostic and progression biomarker of CRC. On the other hand, miR-940 which targets SERPINH1 could be used as a potential biomarker of CRC. More ever, Andecaliximab, Carboxylated glucosamine, Marimastat, Tozuleristide, S-3304, Incyclinide, Curcumin, Prinomastat, Demethylwedelolactone, Bevacizumab, Ocriplasmin , and Collagenase clostridium histolyticum were introduced as therapeutic agents for CRC which their therapeutic potential should be evaluated experimentally.