Identification and Validation of a Novel RNA-Binding Protein-Related Gene-Based Prognostic Model for Multiple Myeloma

Abstract

Background: Multiple myeloma (MM) is a malignant hematopoietic disease that is usually incurable. RNA-binding proteins (RBPs) are involved in the development of many tumors, but their prognostic significance has not been systematically described in MM. Here, we developed a prognostic signature based on eight RBP-related genes to distinguish MM cohorts with different prognoses. Method: After screening the differentially expressed RBPs, univariate Cox regression was performed to evaluate the prognostic relevance of each gene using The Cancer Genome Atlas (TCGA)-Multiple Myeloma Research Foundation (MMRF) dataset. Lasso and stepwise Cox regressions were used to establish a risk prediction model through the training set, and they were validated in three Gene Expression Omnibus (GEO) datasets. We developed a signature based on eight RBP-related genes, which could classify MM patients into high- and low-score groups. The predictive ability was evaluated using bioinformatics methods. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and gene set enrichment analyses were performed to identify potentially significant biological processes (BPs) in MM. Result: The prognostic signature performed well in the TCGA-MMRF dataset. The signature includes eight hub genes: HNRNPC, RPLP2, SNRPB, EXOSC8, RARS2, MRPS31, ZC3H6, and DROSHA. Kaplan–Meier survival curves showed that the prognosis of the risk status showed significant differences. A nomogram was constructed with age; B2M, LDH, and ALB levels; and risk status as prognostic parameters. Receiver operating characteristic (ROC) curve, C-index, calibration analysis, and decision curve analysis (DCA) showed that the risk module and nomogram performed well in 1, 3, 5, and 7-year overall survival (OS). Functional analysis suggested that the spliceosome pathway may be a major pathway by which RBPs are involved in myeloma development. Moreover, our signature can improve on the R-International Staging System (ISS)/ISS scoring system (especially for stage II), which may have guiding significance for the future. Conclusion: We constructed and verified the 8-RBP signature, which can effectively predict the prognosis of myeloma patients, and suggested that RBPs are promising biomarkers for MM.