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.
Highlights
Pancreatic adenocarcinoma (PAAD) is one of the malignant tumors with the worst prognosis in the digestive system
All of eight RNA-binding proteins (RBPs) were related with overall survival of pancreatic adenocarcinoma (PAAD) patients
Of the 173 PAAD patients, the pathologic stage mainly focused on the G2 stage (n = 93, 53.76%) and G3 stage (n = 46, 26.59%); the clinical stage mainly concentrated on stage II (n = 142, 82.08%)
Summary
Pancreatic adenocarcinoma (PAAD) is one of the malignant tumors with the worst prognosis in the digestive system. On the background of great advances in diagnosis and therapy of PAAD, there are only 2–9% of PAAD patients surviving for more than 5 years, indicating that PAAD is a highly fatal disease with an insidious onset (McGuigan et al, 2018) Existing medical technologies such as imaging examination, tumor molecular biomarkers, and pathological examination are currently quite limited and in low efficiency, which may be a momentous reason for low early detection rate and high mortality in PAAD. 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
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