{"title":"遗传和转录的见解揭示丙型肝炎病毒是肾癌的驱动因素。","authors":"Qiankun Wang, Yi Wang, Tongxin Yin, Yuting Feng, Huihao Ren, Xiao Xiao, Jiaoyuan Li, Liming Cheng","doi":"10.1186/s13027-025-00693-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Observational studies suggest a potential link between Hepatitis C virus (HCV) infection and extrahepatic cancers, but the causal relationship remains unclear.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The present study provides evidence supporting a causal link between HCV infection and the development of kidney cancer.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"20 1","pages":"63"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406469/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetic and transcriptional insights reveal hepatitis C virus as a driver of kidney cancer.\",\"authors\":\"Qiankun Wang, Yi Wang, Tongxin Yin, Yuting Feng, Huihao Ren, Xiao Xiao, Jiaoyuan Li, Liming Cheng\",\"doi\":\"10.1186/s13027-025-00693-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Observational studies suggest a potential link between Hepatitis C virus (HCV) infection and extrahepatic cancers, but the causal relationship remains unclear.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The present study provides evidence supporting a causal link between HCV infection and the development of kidney cancer.</p>\",\"PeriodicalId\":13568,\"journal\":{\"name\":\"Infectious Agents and Cancer\",\"volume\":\"20 1\",\"pages\":\"63\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406469/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Infectious Agents and Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13027-025-00693-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious Agents and Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13027-025-00693-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Genetic and transcriptional insights reveal hepatitis C virus as a driver of kidney cancer.
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.
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.
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