Abstract
ObjectiveIncreasing evidence shows that dysregulated RNA binding proteins (RBPs) modulate the progression of several malignancies. Nevertheless, their clinical implications of RBPs in HBV-related hepatocellular carcinoma (HCC) remain largely undefined. Here, this study systematically analyzed the associations of RBPs with HBV-related HCC prognosis.MethodsBased on differentially expressed RBPs between HBV-related HCC and control specimens, prognosis-related RBPs were screened by univariate analyses. A LASSO model was then created. Kaplan-Meier curves, ROCs, multivariate analyses, subgroup analyses and external verification were separately applied to assess the efficacy of this model in predicting prognosis and recurrence of patients. A nomogram was created by incorporating the model and clinical indicators, which was verified by ROCs, calibration curves and decision curve analyses. By CIBERSORT algorithm, the association between the risk score and immune cell infiltrations was evaluated.ResultsTotally, 54 RBPs were distinctly correlated to prognosis of HBV-related HCC. An 11-RBP model was created, containing POLR2L, MRPS12, DYNLL1, ZFP36, PPIH, RARS, SRP14, DDX41, EIF2B4, and NOL12. This risk score sensitively and accurately predicted one-, three- and five-year overall survival, disease-free survival, and progression-free interval. Compared to other clinical parameters, this risk score had the best predictive efficacy. Also, the clinical generalizability of the model was externally verified in the GSE14520 dataset. The nomogram may predict patients’ survival probabilities. Also, the risk score was related to the components in the immune microenvironment.ConclusionCollectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision.
Highlights
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and represents a common malignant neoplasm globally (Liu et al, 2019)
Totally, 54 RNA-binding protein (RBP) were distinctly correlated to prognosis of hepatitis B virus (HBV)-related HCC
Collectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision
Summary
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and represents a common malignant neoplasm globally (Liu et al, 2019). The epidemiology of HCC is affected by underlying liver diseases especially hepatitis B virus (HBV) (Chabrolles et al, 2020). It has been estimated that HBV infection is responsible for 50% of HCC worldwide (Li et al, 2019). HBV that integrates into cancer-relevant genes may drive hepatocarcinogenesis (Nakagawa et al, 2019). The mechanism by which HBV infection contributes to HCC remain deficiently expounded (Torresi et al, 2019). The extensive decrease in HCC cases demands a broader range of universal HBV vaccination application and efficient therapy of HBVrelevant chronic hepatitis, which has a long way to go (Sagnelli et al, 2020)
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