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系统分析确定了一种用于预测和风险调整乙型肝炎病毒相关肝细胞癌预后的特定RNA结合蛋白相关基因模型。

Systematic Analysis Identifies a Specific RNA-Binding Protein-Related Gene Model for Prognostication and Risk-Adjustment in HBV-Related Hepatocellular Carcinoma.

作者信息

Li Maoshi, Liu Zhongwei, Wang Jing, Liu Huimin, Gong Hongmei, Li Shilian, Jia Ming, Mao Qing

机构信息

Department of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, China.

Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.

出版信息

Front Genet. 2021 Aug 4;12:707305. doi: 10.3389/fgene.2021.707305. eCollection 2021.

Abstract

OBJECTIVE

Increasing 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.

METHODS

Based 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.

RESULTS

Totally, 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.

CONCLUSION

Collectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision.

摘要

目的

越来越多的证据表明,失调的RNA结合蛋白(RBPs)可调节多种恶性肿瘤的进展。然而,RBPs在乙型肝炎病毒相关肝细胞癌(HBV相关HCC)中的临床意义仍 largely undefined。在此,本研究系统分析了RBPs与HBV相关HCC预后的相关性。

方法

基于HBV相关HCC与对照样本之间差异表达的RBPs,通过单因素分析筛选出与预后相关的RBPs。然后建立LASSO模型。分别应用Kaplan-Meier曲线、ROC曲线、多因素分析、亚组分析和外部验证来评估该模型预测患者预后和复发的疗效。通过纳入该模型和临床指标创建列线图,并通过ROC曲线、校准曲线和决策曲线分析进行验证。通过CIBERSORT算法评估风险评分与免疫细胞浸润之间的关联。

结果

总共54种RBPs与HBV相关HCC的预后显著相关。创建了一个包含POLR2L、MRPS12、DYNLL1、ZFP36、PPIH、RARS、SRP14、DDX41、EIF2B4和NOL12的11-RBP模型。该风险评分敏感且准确地预测了1年、3年和5年的总生存期、无病生存期和无进展生存期。与其他临床参数相比,该风险评分具有最佳的预测效果。此外,该模型的临床可推广性在GSE14520数据集中得到了外部验证。列线图可预测患者的生存概率。此外,风险评分与免疫微环境中的成分有关。

结论

总的来说,RBPs可能是HBV相关HCC恶性进展的关键因素,对预后和治疗决策具有潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/439e/8371711/0609c593f36f/fgene-12-707305-g001.jpg

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