{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T21:47:25Z","timestamp":1787780845079,"version":"build-2784847793"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T00:00:00Z","timestamp":1665273600000},"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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high\u2010risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The multivariate Cox proportional hazards regression was used to select recurrence\u2010related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT\u2010PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence\u2010free survival (RFS). Then, the recurrence\u2010related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR\u00a0=\u00a01.347; 95% CI\u00a0=\u00a01.012\u20131.793; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.041), ULBP3 (HR\u00a0=\u00a00.453; 95% CI\u00a0=\u00a00.231\u20130.889; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.021) and ULBP5 (HR\u00a0=\u00a03.617; 95% CI\u00a0=\u00a01.819\u20137.194; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) were significantly correlated with RFS in the TCGA\u2010LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low\u2010risk and high\u2010risk subgroups by the predictive score. Compared with the low\u2010risk group, the high\u2010risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low\u2010risk patients with the G1\u2010G2 stage, the levels of infiltrated NK\u2010activated cells and NKG2D expression were both lower in the high\u2010risk patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5318","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T11:41:16Z","timestamp":1665402076000},"page":"6337-6347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A signature based on <scp>NKG2D<\/scp> ligands to predict the recurrence of hepatocellular carcinoma after radical resection"],"prefix":"10.1002","volume":"12","author":[{"given":"Dongbo","family":"Chen","sequence":"first","affiliation":[{"name":"Peking University People's Hospital, Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for liver Disease  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Ren","sequence":"additional","affiliation":[{"name":"Peking University People's Hospital, Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for liver Disease  Beijing China"},{"name":"Laboratory of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Guilin Medical University  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Chen","sequence":"additional","affiliation":[{"name":"Peking University People's Hospital, Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for liver Disease  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yang","sequence":"additional","affiliation":[{"name":"Peking University People's Hospital, Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for liver Disease  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoping","family":"She","sequence":"additional","affiliation":[{"name":"Peking University People's Hospital, Peking University Hepatology Institute Beijing Key Laboratory of Hepatitis C and Immunotherapy for liver Disease  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Hong Kong China"},{"name":"Da Ren Biotech Limited  Hong Kong 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