Application Of Weighted Gene Co-expression Network Analysis To Explore The Potential Diagnostic Biomarkers For Colorectal Cancer And Preliminarily Verify

Colorectal cancer(CRC)is one of the most common malignancies in the world.Many scholars at home and abroad have done a lot of research on the molecular mechanism of CRC and produced a large amount of data.We use a combination of data mining and molecular experiments to look for potential disease-causing genes.It provides reference for the study of molecular mechanism of colorectal cancer.Firstly,the weighted gene co-expression network analysis(WGCNA)was performed for the Gene Expression Omnibus(GEO)dataset GSE87211.In order to analyze the key modules involved in the pathogenesis of CRC,we analyzed the correlation between the gene co-expression modules and the clinical information.Next,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on the key module genes to analyze the functional pathways.The hub genes were screened using the Cytoscape platform.In addition,we carried out preliminary verification of hub genes and discussed the molecular mechanism of CRC.Finally,2 key modules(the green and brown modules)may regulate the occurrence and development of CRC through the extracellular matrix(EMC)pathway,PI3K-Akt and chemokine signaling pathways,thus providing a reference for understanding the complex mechanism of tumorigenesis in CRC.In the present study,10 hub genes were identified in 2 key modules as the genes most significantly associated with the tumorigenesis of CRC.The 5 hub genes from the green module included collagen type I alpha 1 chain(COL1A1),collagen type XII alpha 1 chain(COL12A1),collagen triple helix repeat containing 1(CTHRC1),inhibin subunit beta a(INHBA),and chromobox 2(CBX2),while the 5 hub genes from the brown module included carbonic anhydrase 2(CA2),glucagon(GCG),solute carrier family 4 member 4(SLC4A4)and gliomedin(GLDN),bestrophin 2(BEST2).For BEST2 and CBX2 genes,preliminary molecular level verification shows that BEST2 can affect key genes of Notch pathway that play a role in CRC.However,CBX2 showed different changes in colorectal cancer tissues in AKT and P21,the key genes in the PI3K-AKT pathway that regulate the occurrence and development of CRC.In order to better understand the molecular mechanisms of CRC,we recommend that these genes be further validated by further molecular mechanisms and experiments,while considering the validation in large-scale population.