{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:27:35Z","timestamp":1789450055544,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The number of new cases of hepatocellular carcinoma (HCC) worldwide reached 910,000, ranking the sixth, 80% HCC is associated with viruses, so exploring the molecular mechanism of viral carcinogenicity is imperative. The study showed that both HBV and HCV associated HCC and non-viral HCC have the same molecular phenotype (low gene expression and inhibition of immune pathways), but in the tumor immune micro-environment, there is excessive M2-type macrophage polarization in virus-associated hepatocellular carcinoma. To address this phenomenon, the data sets were analyzed and identified five hub genes (POLR2A, POLR2B, RPL5, RPS6, RPL23A) involved in viral gene expression and associated with PI3K-Akt-mTOR pathway activation by six algorithms. In addition, numerous studies have reported that M2-type macrophages participate in the hepatic fibro-pathological process of the development of HCC and are regulated by the PI3K-Akt-mTOR pathway. On this basis, the study showed that hepatitis virus causes abnormal expression of hub genes, leading to the activation of the pathway, which in turn promote the differentiation of M2-type macrophages and eventually promote the formation of liver fibrosis, leading to the occurrence of HCC. In addition, these hub genes are regulated by transcription factors and m<jats:sup>6<\/jats:sup>A enzyme, and have good prognosis and diagnostic value. With regard to drug reuse, the results suggest that patients with virus-related HCC for whom Cytidine triphosphate disodium salt and Guanosine-5\u2019-Triphosphate are used as supplementary therapy, and may have a better prognosis. In conclusion, the study has identified novel molecules that are carcinogenic to hepatitis viruses and are expected to serve as molecular markers and targets for diagnosis and treatment.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1032819","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T04:41:44Z","timestamp":1668141704000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yong-Zheng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Zeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Feng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2018.06.01","article-title":"Liver cancer incidence and mortality in China: temporal trends and projections to 2030","volume":"30","author":"Zheng","year":"2018","journal-title":"Chin J Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/s2468-1253(22)00124-8","article-title":"Global, regional, and national burden of hepatitis b, 1990-2019: a systematic analysis for the global burden of disease study 2019","volume":"7","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/cej.0000000000000428","article-title":"Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors","volume":"27","author":"Baecker","year":"2018","journal-title":"Eur J Cancer Prev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/978-981-10-5765-6_2","article-title":"Hepatitis b virus-associated hepatocellular Carcinoma. 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