{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T09:09:44Z","timestamp":1772356184213,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer deaths with a dismal 5\u2010year survival rate. The mitogen\u2010activated protein kinase (MAPK) signaling pathway is abnormally activated in HCC to promote growth and aggressive metastatic potential of cancer cells. Therefore, genetic variants in the MAPK signaling pathway may serve as potential predictors of Hepatitis B virus (HBV)\u2010related HCC survival. In the present study, we performed a two\u2010stage survival analysis to evaluate the associations between 10,912 single nucleotide polymorphisms (SNPs) in 79 <jats:italic>MAPK<\/jats:italic> signaling pathway genes and the overall survival (OS) of 866 HBV\u2010related HCC patients, followed by functional annotation. In combined datasets, we identified two novel and potential functional SNPs (<jats:italic>RPS6KA4<\/jats:italic> rs600377 T&gt;G and <jats:italic>MAP2K5<\/jats:italic> rs17300363 A&gt;C) as prognostic factors for HBV\u2010related HCC, with adjusted allelic hazards ratios of 1.24 (95% confidence interval [CI]\u2009=\u20091.05\u20131.46, <jats:italic>p<\/jats:italic>\u2009=\u20090.010) and 1.48 (1.15\u20131.91, <jats:italic>p<\/jats:italic>\u2009=\u20090.001), respectively. Furthermore, their combined risk genotypes also predicted a poor survival in a dose\u2013response manner in the combined data set (<jats:italic>P<\/jats:italic><jats:sub>trend<\/jats:sub>\u2009&lt;\u20090.001). Additional functional analysis showed that <jats:italic>RPS6KA4<\/jats:italic> rs600377 G and <jats:italic>MAP2K5<\/jats:italic> rs17300363 C alleles were associated with elevated mRNA expression levels of the corresponding genes in normal tissues. These results provide new insights into the role of genetic variants in the <jats:italic>MAPK<\/jats:italic> signaling pathway genes in HBV\u2010related HCC survival.<\/jats:p>","DOI":"10.1002\/mc.23583","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T02:14:53Z","timestamp":1686190493000},"page":"1378-1387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potentially functional genetic variants in <i>RPS6KA4<\/i> and <i>MAP2K5<\/i> in the MAPK signaling pathway predict HBV\u2010related hepatocellular carcinoma survival"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-0768","authenticated-orcid":false,"given":"Moqin","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Respiratory Oncology Guangxi Medical University Cancer Hospital Nanning 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