Biological functions and prognostic value of RNA Binding Proteins in clear cell Renal Cell Carcinoma

Abstract

Early detection and accurate evaluation were both critical to improving the prognosis of clear cell Renal Cell Carcinoma (ccRCC) patients. More importantly, RNA Binding Proteins (RBPs) play a vital role in the tumorigenesis and progression of numerous cancers. However, the relationship between RBPs and ccRCC is still unclear. Exploring the potential biological functions of RBPs in ccRCC and establishing a prognostic signature to predict the survival probability remains meaningful. In this study, transcriptome profiling and the corresponding clinical information were obtained from the TCGA database, GEO database, and ICGC database. By using the "edgeR" R package, 200 DERBPs were found, including 128 up-regulated and 72 down-regulated RBPs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DERBPs were mainly involved in regulating transcriptional processes and metabolism. Furthermore, there were 4 hub genes (RPS2, RPS14, RPS20, and RPLP0) were found in the PPI network, which may play vital biological roles among those DERBPs. Then we used LASSO regression to construct a prognostic signature and validated the signature in the GEO and ICGC cohort. The time-dependent receiver operating characteristic (ROC) curve showed that the signature could accurately predict the prognosis of ccRCC patients. Then we established a nomogram, and the calibration curve and ROC curve showed that the nomogram could accurately predict 1-year, 3-year, and 5-year overall survival (OS) of ccRCC patients (The AUC value: 0.871, 0.829, and 0.816). In conclusion, we constructed a 10-RBPs-based prognostic signature integrating clinical parameters to predict the prognosis of ccRCC patients. The prognostic signature based on the differentially expressed RBPs (DERBPs) might serve as promising diagnostic and prognostic biomarkers in ccRCC.

AC010973.2 promotes cell proliferation and is one of six stemness-related genes that predict overall survival of renal clear cell carcinoma

“…Renal clear cell carcinoma (ccRCC), specifically its metastatic form, cause high morbidity and mortality among renal cell carcinoma patients 1 . Tumor stemness-associated genes, small copies of tumor genes, promote tumor initiation, invasion, metastasis, and chemical resistance 14 . Several studies indicate that tumor stemness-associated cells are characterized by unlimited proliferation tendency and multiple differentiation potential, playing an essential vital role in developing multi-drug resistance and tumor recurrence 15 , 16 .…”

AC010973.2 Promotes Cell Proliferation and Is One of Six Stemness-Related Genes That Predict Overall Survival of Renal Clear Cell Carcinoma

“…Altogether, these results indicated that AC010973.2 might promote tumor growth and survival through negatively regulating apoptosis in ccRCC. Discussion ccRCC, especially metastatic ccRCC, demonstrated high morbidity and mortality in renal cell carcinoma patients 13 . Tumor stemness-associated genes, a small copies of tumor genes, were contributed to tumor initiation, invasion, metastasis and chemical resistance 14 .…”

Increased expression of the RNA-binding protein Musashi-2 is associated with immune infiltration and predicts better outcomes in ccRCC patients

“…Recent studies have also indicated that the abnormal expression of some RBPs is involved in the occurrence, proliferation, metastasis, and progression of ccRCC (10-13). Furthermore, prognostic models related to RBPs have also been investigated with database data, which may provide a way to predict the prognosis of ccRCC (14)(15)(16)(17)(18). However, the precise roles of RBPs in ccRCC tumorigenesis and development remain unknown.…”

“…The RBP Musashi-2, a member of the Musashi gene family, has been characterized as an oncoprotein in a variety of tumors, and its aberrant expression is closely associated with tumor occurrence and progression (including in breast, lung, pancreatic, liver, prostate and colorectal cancers) (19)(20)(21)(22)(23)(24) mediated by its participation in the regulation of various molecules and signaling pathways (25). Although some studies that comprehensively analyzed RBPs have shown that multiple prediction models based on RBPs have important guiding significance for the outcome of ccRCC, it is worth noting that these studies were based on increased expression levels of RBPs (15)(16)(17)(18). However, the role and function of Musashi-2 in RCC, particularly in ccRCC, are still not clear, and there are currently no studies on the effects of the RBP Musashi-2 on ccRCC patients.…”