Development and validation of a prognostic 9-gene signature for colorectal cancer

Colorectal cancer (CRC) is one of the most prevalent cancers globally with a high mortality rate. Predicting prognosis using disease progression and cancer pathologic stage is insufficient, and a prognostic factor that can accurately evaluate patient prognosis needs to be developed. In this study, we aimed to infer a prognostic gene signature to identify a functional signature associated with the prognosis of CRC patients.

First, we used univariate Cox regression, least absolute shrinkage and selection operator (lasso) regression, and multivariate Cox regression analyses to screen genes significantly associated with CRC patient prognosis, from colorectal cancer RNA sequencing data in The Cancer Genome Atlas (TCGA) database. We then calculated the risk score (RS) for each patient based on the expression of the nine candidate genes and developed a prognostic signature.

Based on the optimal cut-off on the receiver operating characteristic (ROC) curve, patients were separated into high- and low-risk groups, and the difference in overall survival between the two groups was examined. Patients in the low-risk group had a better overall survival rate than those in the high-risk group. The results were validated using the GSE72970, GSE39582, and GSE17536 Gene Expression Omnibus (GEO) datasets, and the same conclusions were reached. ROC curve test of the RS signature also indicated that it had excellent accuracy. The RS signature was then compared with traditional clinical factors as a prognostic indicator, and we discovered that the RS signature had superior predictive ability.

The RS signature developed in this study has excellent predictive power for the prognosis of patients with CRC and broad applicability as a prognostic indicator for patients.