A five-gene based risk score with high prognostic value in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC. The GSE14333 dataset containing survival information was then introduced in order to screen and verify prognosis-associated genes. Of the 66 DEGs, the present study screened out 46 biomarkers closely associated to patient overall survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was demonstrated that these genes participated in multiple biological processes which were highly associated with cancer proliferation, drug-resistance and metastasis, thus further affecting patient survival. The five most important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium voltage-gated channel a subunit 9 were selected by a random survival forests algorithm, and were further made up to a linear risk score formula by multivariable cox regression. Finally, the present study tested and verified this risk score within three indepen dent GEO datasets (GSE14333, GSE17536 and GSE29621), and observed that patients with a high risk score had a lower overall survival (P<0.05). Furthermore, this risk score was the most significant compared with other predicting factors including age and American Joint Committee on Cancer stage, in the model, and was able to predict patient survival independently and directly. The findings suggest that this survival associated DEGs-based risk score is a powerful and accurate prognostic tool and is promisingly implemented in a clinical setting.