Construction of an RNA-Binding Protein-Related Prognostic Model for Pancreatic Adenocarcinoma Based on TCGA and GTEx Databases

Abstract

Background: Recently, RNA-binding proteins (RBPs) were reported to interact with target mRNA to regulate gene posttranscriptional expression, and RBP-mediated RNA modification can regulate the expression and function of proto-oncogenes and tumor suppressor genes. We systematically analyzed the expression of RBPs in pancreatic adenocarcinoma (PAAD) and constructed an RBP-associated prognostic risk model.Methods: Gene expression data of normal pancreatic samples as well as PAAD samples were downloaded from TCGA-PAAD and GTEx databases. Wilcoxon test and univariate Cox analysis were, respectively, applied to screen differential expression RBPs (DE-RBPs) and prognostic-associated RBPs (pRBPs). Functional enrichment was analyzed by GO, KEGG, and GSEA. Protein–protein interaction (PPI) network was constructed by STRING online database. Modeling RBPs were selected by multivariate Cox analysis. Kaplan–Meier survival and Cox analysis were applied to evaluate the effects of risk score on the overall survival of PAAD patients. ROC curves and validation cohort were applied to verify the accuracy of the model. Nomogram was applied for predicting 1-, 3-, and 5-year overall survival (OS) of PAAD patients. At last, modeling RBPs were further analyzed to explore their differential expression, prognostic value, as well as enrichment pathways in PAAD.Results: RBPs (453) were differentially expressed in normal and tumor samples, besides, 28 of which were prognostic associated. DE-RBPs (453) are functionally associated with ribosome, ribonuclease, spliceosome, etc. Eight RBPs (PABPC1, PRPF6, OAS1, RBM5, LSM12, IPO7, FXR1, and RBM6) were identified to construct a prognostic risk model. Higher risk score not only predicted poor prognosis but also was an independent poor prognostic indicator, which was verified by ROC curves and validation cohort. Eight modeling RBPs were confirmed to be significantly differentially expressed between normal and tumor samples from RNA and protein level. Besides, all of eight RBPs were related with overall survival of PAAD patients.Conclusions: We successfully constructed an RBP-associated prognostic risk model in PAAD, which has a potential clinical application prospect.

Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

“…As RBPs play an instrumental role in regulating normal cellular processes, the altered expression of RBP emerged as a major player in the development and progression of cancer. Apart from candidate RBP studies and their involvement in pancreatic cancer, there are very few reports of universal RBPome studies derived from TCGA RNA-sequencing data in pancreatic cancer which have discrepancies between the results ( Glass et al, 2020 ; Wen et al, 2020 ). Disparity among the outcomes of these studies led us to investigate the RBPs which are universally altered in pancreatic cancer.…”

ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway

“…The expression level of ITGB5 in different types of tumors was obtained from the GEPIA website (http://gepia.cancerpku.cn/) (24). Gene expression data of PAAD were downloaded and processed from TCGA-PAAD (https://portal.gdc.cancer.gov/) and GTEx (https:// xenabrowser.net/datapages/) databases as in our previous study (25). Simply, a total of 171 normal pancreatic samples (167 from GTEx and four from TCGA) and 178 PAAD samples were used to analyze the ITGB5 expression difference.…”

Construction of a five-gene prognostic model based on immune-related genes for the prediction of survival in pancreatic cancer

“…Their expression was up-regulated in PC tissues and was associated with poor prognosis [ 26 ]. Similarly, from the perspective of RNA-binding proteins, a close relationship between OAS1 and the prognosis of PC was also found [ 27 ]. Guanylate-binding protein 2 (GBP2) is a guanylate-binding protein involved in response to viral or microbial infection; it is induced by Type I and Type II interferons.…”