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Immunotherapy is assuming a role as a pillar of HCC treatment, but the remarkable immune\u2010mediated responses are restricted in a minority of patients. Nucleic acid sensing (NAS) pathways are the central pathway of the innate immune system and antiviral immune response to viral infection, but their role in hepatitis virus\u2010related HCC remains undetermined. In our study, we performed a comprehensive bioinformatics analysis based on transcriptomic data of hepatitis virus related\u2010HCC\u00a0tissues collected from multiple public data sets. Two subgroups were validated based on NAS\u2010related\u00a0genes in virus\u2010related HCC patients, which were defined as NAS\u2010activated\u00a0subgroups and NAS\u2010suppressed subgroups based on the expression of NAS\u2010related genes. On this basis, a NAS\u2010related risk score (NASRS) predictive model was established for risk stratification and prognosis prediction in the hepatitis virus\u2010related HCC (TCGA\u2010LIHC\u00a0and ICGC cohorts). The predictive values of the NASRS in prognosis and immunotherapy were also verified in multiple data sets. A nomogram was also established to facilitate the clinical use of NASRS and demonstrate its effectiveness through different approaches. Additionally, six potential drugs binding to the core target of the NAS signature were predicted via molecular docking strategy. We subsequently evaluated the cytotoxic capabilities of potential drug in vitro and in vivo. Based on these results, we conclude that the NASRS model could serve as a power prognostic biomarker and predict responses to immunotherapy, which is meaningful in clinical decision\u2010making of hepatitis virus\u2010related HCC patients.<\/jats:p>","DOI":"10.1002\/jmv.29084","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T13:04:17Z","timestamp":1695042257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Establishment of nucleic acid sensing pathways\u2010based model in predicting response to immunotherapy and targeted drug in hepatitis virus\u2010related hepatocellular carcinoma"],"prefix":"10.1002","volume":"95","author":[{"given":"Xinhao","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"},{"name":"Department of Oncology The 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