Introduction: Colorectal cancer (CRC) originates from mutations in the epithelial tissues of the colon and the rectum. CRC is the third most common cancer in the world and the second leading cause of cancer-related deaths. Colorectal cancer is affected by several genetic factors, such as silencing of tumor suppressor genes and genes participating in cell cycle regulation. Environmental factors also have different effects on this cancer, including obesity, unhealthy eating habits, increasing age, and smoking. Long non-coding RNAs (lncRNAs) have regulatory effects on gene expression in CRC. In this study, with the use of different bioinformatics analyses, the aim is to identify biomarkers related to this cancer.
Methods: Microarray analysis was performed on GSE110223 in the field of colorectal cancer from the GEO database, and after GEO2R analysis, a gene was selected with a significant upregulation.
Gene expression and survival analysis of the said gene were checked in COAD and READ using GEPIA2. The TCGA database was used to check mutations and CNVs of the gene in different cancers. The signaling pathways in which the selected gene was active were checked by KEGG. The protein-protein interactions of the gene were analyzed using STRING. Subsequently, the miRNAs related to the gene were extracted from TargetScan and miRTarBase, and common miRNAs were selected using Cytoscape. Finally, the lncRNAs associated with the common miRNAs were collected from LncBase (DIANA) and common lncRNAs were found using Cytoscape.
Results: Gene INHBA (LogFC=1.843, adj p-value = 0.000194) was selected from GSE110223 as an upregulated gene in CRC. As expected, the dot plot revealed significant overexpression of the gene in COAD and READ. Survival analysis showed that high expression of INHBA significantly reduces overall survival of individuals. Subsequently, among the common miRNAs from databases, two lncRNAs (AC1144910.1 and AC009646.1) were found to be the biomarkers associated with CRC.
Conclusion: According to KEGG Pathways (map04350 and map05210), this gene may lead to the loss of growth inhibitory effects of TGFβ resulting in excessive cell growth. The INHBA gene and its two common lncRNAs indicate the important role of this gene in colorectal cancer and Cancer progression can occur by the overexpression of INHBA. Accordingly, using these biomarkers can help with early diagnosis and the development of treatments for CRC.
Keywords: Colorectal Cancer
miRNA
lncRNA
Bioinformatics
Biomarkers
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