{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:52:56Z","timestamp":1791129176849,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574179"],"award-info":[{"award-number":["82574179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The poor prognosis of liver cancer (LC) highlights the urgent need for more effective strategies for early detection. We conducted a large, multicenter study to develop and validate a serum metabolic signature for LC diagnosis. Using high\u2010throughput nanoparticle\u2010enhanced laser desorption\/ionization mass spectrometry, we profiled serum metabolites from 1,924 participants in discovery cohort recruited across 11 clinical centers and 225 participants in independent external validation cohort from two additional centers. A nine\u2010metabolite signature combined with alpha\u2010fetoprotein achieved excellent discriminatory performance, with an AUC of 0.92 in the discovery cohort and 0.93 in the external validation cohort. The combined model also showed good sensitivity for early\u2010stage LC, reaching 0.85 and 0.78 in the two cohorts, respectively, and performed particularly well for hepatocellular carcinoma, with AUCs of 0.94 and 0.93. Exploratory analyses suggested potential utility for intrahepatic cholangiocarcinoma diagnosis. Mendelian randomization analysis supported a potential causal association between nicotinamide (NAM) levels and LC risk. Functional studies showed that NAM promotes LC cell proliferation, migration, and invasion, through an NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/SIRT1\u2010dependent mechanism that increases HIF1\u03b1 stability and activates glycolytic and MAPK signaling. Overall, we developed a promising metabolic diagnostic signature for LC and identified NAM\u2010associated metabolic signaling as a potential contributor to LC progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.78077","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:38:15Z","timestamp":1791128295000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Signatures for Liver Cancer Diagnosis and Mechanistic Insights: A Large\u2010Scale, Multicenter Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8417-3168","authenticated-orcid":false,"given":"Yongjie","family":"Xu","sequence":"first","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6846-7550","authenticated-orcid":false,"given":"Jiachen","family":"Wang","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3930-9146","authenticated-orcid":false,"given":"Chunmeng","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9097-1369","authenticated-orcid":false,"given":"Changfa","family":"Xia","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyong","family":"Liu","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital &amp; Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9576-1106","authenticated-orcid":false,"given":"Yuanjie","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Chang","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital &amp; Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaokai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control Henan International Joint Laboratory of Cancer Prevention  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-1671","authenticated-orcid":false,"given":"Yutong","family":"He","sequence":"additional","affiliation":[{"name":"Cancer Institute the Fourth Hospital of Hebei Medical University\/the Tumor Hospital of Hebei Province  Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4791-3734","authenticated-orcid":false,"given":"Ruifang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Tumor Biobank, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University  Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Xi","sequence":"additional","affiliation":[{"name":"The Inner Mongolia Autonomous Region Center for Disease Control and Prevention  Inner Mongolia China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-4314","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Senior Department of Infectious Diseases\/National Clinical Research Center for Infectious Diseases Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-1965","authenticated-orcid":false,"given":"Kun","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-1884","authenticated-orcid":false,"given":"Wanqing","family":"Chen","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"issue":"10504","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0140-6736(25)01042-6","article-title":"The Lancet Commission on Addressing the Global Hepatocellular Carcinoma Burden: Comprehensive Strategies From Prevention to Treatment","volume":"406","author":"Chan S. 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