Development and validation of a six-RNA binding proteins prognostic signature and candidate drugs for prostate cancer.

ABSTRACT

The dysregulation of RNA binding proteins (RBPs) regulates the progression of several cancers. However, information on the overall functions of RBPs in prostate cancer (PCa) remains largely understudied. Therefore, based on the TCGA dataset, this study identified 144 differentially expressed RBPs in tumors compared to normal tissues. Subsequently, through univariate, LASSO and multivariate Cox regression analysis, 6 RBP genes among them, MSI1, MBNL2, LENG9, REXO2, RNASE1, and PABPC1L were screened as prognostic hub genes and prognostic signature was further identified. Further analysis indicated that the high-risk group was significantly associated with poor RFS, which was validated in the MSKCC cohort. Besides, patients in the high-risk group were closely associated with dysregulation of DNA damage repair pathway, copy number alteration, tumor burden mutation, and low-response to cisplatin (P < 0.001), and bicalutamide (P < 0.001). Using the Connectivity Map, we finally predicted 3 drugs including, ribavirin, carmustine, and carbenoxolone. In summary, we identified six-RBP gene signature and 3 potential drugs against PCa, which might promote the individualized treatment strategies and further improve the quality of life among PCa patients.