Genetic and transcriptional insights reveal hepatitis C virus as a driver of kidney cancer.

IF 2.8 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2025-09-02 DOI:10.1186/s13027-025-00693-9

Qiankun Wang, Yi Wang, Tongxin Yin, Yuting Feng, Huihao Ren, Xiao Xiao, Jiaoyuan Li, Liming Cheng

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引用次数: 0

Abstract

Objectives: Observational studies suggest a potential link between Hepatitis C virus (HCV) infection and extrahepatic cancers, but the causal relationship remains unclear.

Methods: We applied a two-sample Mendelian randomization (MR) approach to evaluate the causal relationships between HCV infection and various extrahepatic cancers. A two-step MR was used to identify potential mediators, followed by colocalization analysis to identify HCV-associated susceptibility genes (HSGs). A pan-cancer analysis using TCGA data was conducted, and a prognostic model based on HSGs was developed using least absolute shrinkage and selection operator (LASSO) regression and Cox models. Genetic risk score (GRS) analysis from the UK Biobank validated our findings.

Results: We identified a causal link between genetic susceptibility to HCV infection and kidney cancer, both in univariable and multivariable MR analyses. The two-step MR identified five mediators in the causal pathway. IRF5 was highlighted as a key HSG in both the colocalization and pan-cancer analyses. Our prognostic model incorporating three HSGs predicted overall survival (OS) in kidney cancer patients. GRS analysis confirmed the association.

Conclusions: The present study provides evidence supporting a causal link between HCV infection and the development of kidney cancer.

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遗传和转录的见解揭示丙型肝炎病毒是肾癌的驱动因素。

目的：观察性研究提示丙型肝炎病毒（HCV）感染与肝外癌之间存在潜在联系，但因果关系尚不清楚。方法：我们采用双样本孟德尔随机化（MR）方法来评估HCV感染与各种肝外癌之间的因果关系。采用两步磁共振鉴定潜在介质，然后进行共定位分析鉴定hcv相关易感基因（hsg）。使用TCGA数据进行泛癌分析，并使用最小绝对收缩和选择算子（LASSO）回归和Cox模型建立基于hsg的预后模型。英国生物银行的遗传风险评分（GRS）分析证实了我们的发现。结果：在单变量和多变量MR分析中，我们确定了HCV感染的遗传易感性与肾癌之间的因果关系。两步MR确定了因果通路中的五个中介。IRF5在共定位和泛癌分析中都被强调为关键的HSG。我们的预后模型包含三个hsg预测肾癌患者的总生存期（OS）。GRS分析证实了这种关联。结论：本研究提供证据支持HCV感染与肾癌发展之间的因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.