{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:05:54Z","timestamp":1784178354267,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011785","name":"Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation","doi-asserted-by":"publisher","award":["2024GXNSFDA010040"],"award-info":[{"award-number":["2024GXNSFDA010040"]}],"id":[{"id":"10.13039\/501100011785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011827","name":"Innovation Project of Guangxi Graduate Education","doi-asserted-by":"publisher","award":["YCBZ2024134"],"award-info":[{"award-number":["YCBZ2024134"]}],"id":[{"id":"10.13039\/501100011827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011785","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFBA069420"],"award-info":[{"award-number":["2025GXNSFBA069420"]}],"id":[{"id":"10.13039\/501100011785","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Youth Program of Scientific Research Foundation of Guangxi Medical University Cancer Hospital","award":["YQJ2024-09"],"award-info":[{"award-number":["YQJ2024-09"]}]},{"DOI":"10.13039\/501100018925","name":"111 Center","doi-asserted-by":"crossref","award":["D17011"],"award-info":[{"award-number":["D17011"]}],"id":[{"id":"10.13039\/501100018925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Purpose: Nucleotide metabolism plays a critical role in cancer development, but the prognostic significance of genetic variants in nucleotide metabolism genes for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients remains unclear. Methods: We performed Cox proportional hazards regression analyses to evaluate the association between genetic variants in 94 nucleotide metabolism-related genes and overall survival (OS) in 866 HBV-HCC patients. To assess the potential biological relevance of the identified variants, the Bayesian false discovery probability and false-positive report probability were applied for multiple testing correction. Results: Two independent SNPs, DCTD rs17074255 G&gt;A (HR = 1.22, 95% CI: 1.06\u20131.40, p = 0.005) and ENTPD2 rs3763662 G&gt;A (HR = 1.18, 95% CI: 1.03\u20131.34, p = 0.015), were significantly associated with OS. A significant dose-dependent association between the number of risk genotypes and poorer OS was observed (Ptrend &lt; 0.001). Luciferase reporter assays demonstrated allele-specific regulatory effects of rs3763662 on ENTPD2 expression (p &lt; 0.001). DCTD and ENTPD2 mRNA expression levels were significantly elevated in HCC tumors in the UALCAN database and in our 103 paired samples. Higher expression levels of both genes were associated with poorer survival in the TCGA cohort (p = 0.003 and p &lt; 0.001). Conclusions: Our findings suggest that ENTPD2 rs3763662 (supported by direct functional evidence) and DCTD rs17074255 (supported by eQTL and expression associations) may serve as potential prognostic indicators for HBV-HCC through the regulation of mRNA expression. These findings provide new insights into the role of nucleotide metabolism-related genetic variation in HBV-HCC progression and may facilitate prognostic assessment, pending replication in independent cohorts.<\/jats:p>","DOI":"10.3390\/cancers18142253","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:53Z","timestamp":1784023973000},"page":"2253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potentially Functional Variants of DCTD and ENTPD2 in the Metabolism of Nucleotide Pathway Genes Predict Survival of HBV-Related Hepatocellular Carcinoma Patients"],"prefix":"10.3390","volume":"18","author":[{"given":"Yan","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-4345","authenticated-orcid":false,"given":"Qiuling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"},{"name":"Key Laboratory of Cancer Molecular Medicine of Guangxi, 22 Shuangyong Road, Qingxiu District, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-4713","authenticated-orcid":false,"given":"Zihan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9567-0854","authenticated-orcid":false,"given":"Qiuping","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"},{"name":"Key Laboratory of Cancer Molecular Medicine of Guangxi, 22 Shuangyong Road, Qingxiu District, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanji","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institutional Review Board Office, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-9445","authenticated-orcid":false,"given":"Qingyi","family":"Wei","sequence":"additional","affiliation":[{"name":"Cancer Prevention and Treatment Research Institute, Greater Bay Area Institute of Precision Medicine, 6 Nanjiang 2nd Road, Nansha District, Guangzhou 511462, China"},{"name":"Department of Epidemiology, School of Public Health, Fudan University, 130 Dong\u2019an Road, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Human Resources Department, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Qingxiu District, Nanning 530021, China"},{"name":"Key Laboratory of Cancer Molecular Medicine of Guangxi, 22 Shuangyong Road, Qingxiu District, Nanning 530021, China"},{"name":"Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning 530021, China"},{"name":"Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University Cancer Hospital, Nanning 530021, China"},{"name":"Guangxi Zhuang Autonomous Region Molecular Medical Engineering Research Center for Cancer, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 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