Bioinformatics for The Prognostic Value and Function of Cubilin (CUBN) in Colorectal Cancer

BACKGROUND Cubilin (CUBN) gene was reported to be a novel risk variant for colorectal cancer (CRC). Previous studies have shown that germline variants in known cancer driver genes are predictive of patient outcome, but no study has systematically analyzed CRC to identify CUBN that can predict patient outcome and function by using bioinformatics. MATERIAL AND METHODS The association in expression, clinicopathological parameters, and survival were analyzed by using Oncomine, UNCLA, and GEPIA, while CUBN alterations and related functional networks were identified using cBioPortal. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) of CUBN in CRC were explored by using LinkOmics. Gene set enrichment analysis (GSEA) examined target networks of kinases, miRNAs, and transcription factors. RESULTS We found that CUBN was overexpressed in CRC. Patients who were in advanced TNM stage tended to express higher CUBN mRNA levels, while those who received radiotherapy tended to express relatively lower CUBN mRNA levels. Higher expression of CUBN was found to be associated with shorter overall survival (OS) and disease-free survival (DFS). Moreover, functional networks analysis suggested that CUBN can regulate mismatch repair, terpenoid backbone biosynthesis, base excision repair, and proteasome via vitamin digestion and absorption pathway to influence CRC occurrence. CONCLUSIONS These findings suggested that CUBN could serve as a prognostic and therapeutic biomarker of CRC in the future.