{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T07:01:11Z","timestamp":1756191671347,"version":"3.41.2"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)\u2010related HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway\u2010related genes and overall survival (OS) of 866 patients with HBV\u2010related HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>It was found that three independent SNPs (<jats:italic>NEURL1B<\/jats:italic> rs4868192, <jats:italic>CNTN1<\/jats:italic> rs444927 and <jats:italic>FCER2<\/jats:italic> rs1990975) were significantly associated with the HBV\u2010related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose\u2010response manner (<jats:italic>p<\/jats:italic><jats:sub>trend<\/jats:sub>\u2009&lt;0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (<jats:italic>p<\/jats:italic>\u2009=\u20090.002) and from 72.04% to 74.76 (<jats:italic>p<\/jats:italic>\u2009=\u20090.004) for 3\u2010year and 5\u2010year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of <jats:italic>NEURL1B<\/jats:italic> in the whole blood (<jats:italic>p<\/jats:italic>\u2009=\u20091.71\u2009\u00d7\u200910<jats:sup>\u20103<\/jats:sup>), while the rs1990975 T allele was correlated with higher mRNA expression levels of <jats:italic>FCER2<\/jats:italic> in the whole blood and normal liver tissues (<jats:italic>p<\/jats:italic>\u2009=\u20093.51\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup> and 0.033, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Three potentially functional SNPs of <jats:italic>NEURL1B<\/jats:italic>, <jats:italic>CNTN1<\/jats:italic> and <jats:italic>FCER2<\/jats:italic> may serve as potential prognostic biomarkers for HBV\u2010related HCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7040","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T06:30:07Z","timestamp":1712039407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus\u2010related hepatocellular carcinoma"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4263-301X","authenticated-orcid":false,"given":"Liming","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Experimental Research Guangxi Medical University Cancer Hospital  Nanning China"},{"name":"Department of Epidemiology and Health Statistics, School of Public Health Guangxi Medical University  Nanning 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