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基于二硫键连接蛋白相关基因探索乙肝病毒相关肝癌患者的预后及治疗策略

Exploring prognosis and therapeutic strategies for HBV-HCC patients based on disulfidptosis-related genes.

作者信息

Zhang Chuankuo, Zhang Xing, Dai Shengjie, Yang Wenjun

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Front Genet. 2025 Jan 15;15:1522484. doi: 10.3389/fgene.2024.1522484. eCollection 2024.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) accounts for over 80% of primary liver cancers and is the third leading cause of cancer-related deaths worldwide. Hepatitis B virus (HBV) infection is the primary etiological factor. Disulfidptosis is a newly discovered form of regulated cell death. This study aims to develop a novel HBV-HCC prognostic signature related to disulfidptosis and explore potential therapeutic approaches through risk stratification based on disulfidptosis.

METHODS

Transcriptomic data from HBV-HCC patients were analyzed to identify BHDRGs. A prognostic model was established and validated using machine learning, with internal datasets and external datasets for verification. We then performed immune cell infiltration analysis, tumor microenvironment (TME) analysis, and immunotherapy-related analysis based on the prognostic signature. Besides, RT-qPCR and immunohistochemistry were conducted.

RESULTS

A prognostic model was constructed using five genes (, , , , and ). A corresponding prognostic nomogram was developed based on riskScores, age, stage. Stratification by median risk score revealed a significant correlation between the prognostic signature and TME, tumor immune cell infiltration, immunotherapy efficacy, and drug sensitivity. The results of the experiments indicate that expression is higher in tumor tissues compared to adjacent tissues. expression is higher in HBV-HCC tumor tissues compared to normal tissues.

CONCLUSION

This study stratifies HBV-HCC patients into distinct subgroups based on BHDRGs, establishing a prognostic model with significant implications for prognosis assessment, TME remodeling, and personalized therapy in HBV-HCC patients.

摘要

背景

肝细胞癌(HCC)占原发性肝癌的80%以上,是全球癌症相关死亡的第三大主要原因。乙型肝炎病毒(HBV)感染是主要病因。二硫化物诱导的细胞焦亡是一种新发现的程序性细胞死亡形式。本研究旨在开发一种与二硫化物诱导的细胞焦亡相关的新型HBV-HCC预后特征,并通过基于二硫化物诱导的细胞焦亡的风险分层探索潜在的治疗方法。

方法

分析HBV-HCC患者的转录组数据以识别BHDRGs。使用机器学习建立并验证预后模型,通过内部数据集和外部数据集进行验证。然后,基于预后特征进行免疫细胞浸润分析、肿瘤微环境(TME)分析和免疫治疗相关分析。此外,还进行了RT-qPCR和免疫组织化学检测。

结果

使用五个基因(、、、和)构建了预后模型。基于风险评分、年龄、分期开发了相应的预后列线图。通过中位风险评分分层显示,预后特征与TME、肿瘤免疫细胞浸润、免疫治疗疗效和药物敏感性之间存在显著相关性。实验结果表明,与相邻组织相比,肿瘤组织中的表达更高。与正常组织相比,HBV-HCC肿瘤组织中的表达更高。

结论

本研究基于BHDRGs将HBV-HCC患者分为不同亚组,建立了一个对HBV-HCC患者的预后评估、TME重塑和个性化治疗具有重要意义的预后模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d1/11774838/eae8a4f1b98a/fgene-15-1522484-g001.jpg

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