Identification and Validation of an RNA Binding Proteins-Associated Prognostic Signature for Non-Small Cell Lung Cancer

Abstract

Background: Non-small cell lung cancer (NSCLC) is a malignancy with relatively high incidence and poor prognosis. RNA-binding proteins (RBPs) were reported to be dysregulated in multiple cancers and were closely associated with tumor initiation and progression. However, the functions of RBPs in NSCLC remain unclear. Method: The RNA sequencing data and corresponding clinical information of NSCLC was downloaded from The Cancer Genome Atlas (TCGA) database. We identified aberrantly expressed RBPs between tumor and control tissue, and systemically investigated the expression and prognostic value of these RBPs by a series of bioinformatics analysis.Results: A total of 459 aberrantly expressed RBPs (291 up-regulated and 168 down-regulated RBPs) were identified. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with RNA splicing, ncRNA metabolic process, regulation of translation, mRNA surveillance pathway, RNA degradation, and RNA transport. Thirteen RBPs (ZC3H12C, ZC3H12D, BOP1, CASC3, DDX24, IGF2BP1, KHDC1, FASTKD3, TARBP1, INTS7, NOL12, SNRPB, PABPC1L) were identified as prognostic RBPs by multivariate Cox regression analysis, and were used to construct a prognostic signature. Further analysis demonstrated that high-risk group were significantly related to poor overall survival in training and testing cohort. The area under receiver operator characteristic curve of the prognostic signature was 0.703 in training cohort and 0.636 in testing cohort. In addition, the prognostic signature was further validated in differently clinical subgroup (>=65, <65, female, male, stage I-II, III- IV, T1-2, T3-4, N0, N1-3, M0 and M1). The risk score was an independent prognostic factor of NSCLC. A nomogram based on thirteen RBPs was constructed to predict the survival of patients.Conclusion: Our results provide novel insights into the pathogenesis of NSCLC. The RBPs-associated prognostic signature showed predictive value for NSCLC prognosis, with potential applications in clinical decision-making and individualized treatment.