The importance of variants and network interactions in the progression of colorectal cancer

: Colorectal cancer(CRC) is the third most common cancer worldwide and the second deadliest. Various factors, such as diet, physical activity, and genetics, play a crucial role in CRC development. Through gene expression studies and association analyses, researchers have identified biomarkers and variants associated with CRC, which helps understand the disease's onset and progression. Current research focused on identifying hub genes and exploring the relationship between gene polymorphisms and interaction with micro-RNAs, and susceptibility to CRC. Method:We analyzed ten GEO (Gene Expression Omnibus) (https://www.ncbi.nlm.nih.gov/geo) datasets and GEPIA (Gene Expression Profiling Interactive Analysis) (http://gepia.cancer-pku.cn) (consisting of ۳۰۱ colorectal tumors and healthy samples) to achieve common differentially expressed genes (DEGs) between colorectal cancer tumors and control tissues. The bioinformatics approach resulted in a final DEG list consisting of ten upregulated genes (logFC ≥|۱| and P < ۰.۰۵). GEPIA۲ Co-expression, STRING (https://string-db.org/) and CYTOSCAPE software network construction indicated the two central hub genes, SPARC and EFTUD۲. We focused on these candidate genes for designing the second phase of the present study, variant selection. The us NCBI's SNP Viewer (https://www.ncbi.nlm.nih.gov/geo/) and miRNASNP database(https://ngdc.cncb.ac.cn/databasecommons/database/id/۱۶۸۱) revealed variants located within the ۳'UTR regions with an essential interaction with several micro-RNAs. Result:According to expression analysis EFTUD۲ and SPARC may play an essential role in susceptibility to colorectal cancer. Also, we found three critical variants including, rs۲۳۰۴۹۸۶ located in the ۳'UTR region of EFTUD۲ gene and rs۴۹۵۸۲۷۸ and rs۱۰۵۹۸۲۹ located in the ۳'UTR region of SPARC gene. The rs۲۳۰۴۹۸۶ affects binding to has-miR-۱۸۸-۳p, rs۱۰۵۹۸۲۹ affects binding to has-miR-۴۸۸-۳p, and rs۴۹۵۸۲۷۸ has the strongest association with has-miR-۵۱۵-۵p. Moreover, according to the HaploReg database, these variants interact with several important transcription factors, such as Roaz and THAP۱ which have increased expression in colorectal cancer. Conclusion:We found genes, variants, micro-RNAs, and transcription factors that may play crucial roles in the development of colorectal cancer. The selected variants could have regulatory impacts on the hub genes expressions by affecting the binding affinity of several microRNAs and transcription factors, suggesting significant pharmacogenetics importance.

کلیدواژه ها:

Colorectal cancer ، Expression analysis and Association study ، Cytoscape ، HaploReg ، miRNASNP