RNA processing genes characterize RNA splicing and further stratify colorectal cancer.

OBJECTIVES

Due to the limited evaluation of the prognostic value of RNA processing genes (RPGs), which are regulators of alternative splicing events (ASEs) that have been shown to be associated with tumour progression, this study sought to determine whether colorectal cancer (CRC) could be further stratified based on the expression pattern of RPGs.

MATERIALS AND METHODS

The gene expression profiles of CRCs were collected from TCGA (training set) and three external validation cohorts, representing 1060 cases totally. Cox regression with least absolute shrinkage and selection operator (LASSO) penalty was used to develop an RNA processing gene index (RPGI) risk score. Kaplan-Meier curves, multivariate Cox regression and restricted mean survival (RMS) analyses were harnessed to evaluate the prognostic value of the RPGI.

RESULTS

A 22-gene RPGI signature was developed, and its risk score served as a strong independent prognostic factor across all data sets when adjusted for major clinical variables. Moreover, ASEs for certain genes, such as FGFR1 and the RAS oncogene family, were significantly correlated with RPGI. Expression levels of genes involved in splicing- and tumour-associated pathways were significantly correlated with RPGI score. Furthermore, a combination of RPGI with age and tumour stage resulted in significantly improved prognostic accuracy.

CONCLUSIONS

Our findings highlighted the prognostic value of RPGs for risk stratification of CRC patients and provide insights into specific ASEs associated with the development of CRC.