Open AccessRNA processing genes characterize RNA splicing and further stratify colorectal cancer
Author(s) -
Lu Xiaofan,
Zhou Yujie,
Meng Jialin,
Jiang Liyun,
Gao Jun,
Cheng Yu,
Yan Hangyu,
Wang Yang,
Zhang Bing,
Li Xiaobo,
Yan Fangrong
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12861
Subject(s) - proportional hazards model , gene , alternative splicing , rna splicing , colorectal cancer , lasso (programming language) , biology , gene expression , oncology , rna , survival analysis , medicine , cancer , messenger rna , genetics , computer science , world wide web
Abstract 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.