{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:15:45Z","timestamp":1788250545187,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP\u201026K02294"],"award-info":[{"award-number":["JP\u201026K02294"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP\u201026K19605"],"award-info":[{"award-number":["JP\u201026K19605"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the prognostic significance of preoperative Mac\u20102 binding protein glycosylation isomer (M2BPGi) and determine whether tumor metabolic activity provides additional risk stratification after hepatic resection for hepatocellular carcinoma (HCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 291 patients with HCC who underwent hepatic resection at a single Japanese institution between 2015 and 2023 and had available preoperative M2BPGi and 18F\u2010fluorodeoxyglucose positron emission tomography\/computed tomography data. Associations with clinicopathological features, recurrence\u2010free survival (RFS), and overall survival (OS) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High M2BPGi was associated with impaired liver function and F3\u2013F4 fibrosis but not with tumor\u2010related features or tumor metabolic activity. In contrast, high tumor metabolic activity was associated with higher des\u2010\n                      <jats:italic>\u03b3<\/jats:italic>\n                      \u2010carboxy prothrombin (DCP) levels, larger tumors, poor differentiation, microscopic vascular invasion, and intrahepatic metastasis. High M2BPGi and high tumor metabolic activity independently predicted worse RFS (hazard ratio [HR], 1.61;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0105 and HR, 1.94;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0023, respectively) and OS (HR, 2.03;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0042 and HR, 1.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0199, respectively). The dual\u2010high group had the poorest RFS and OS (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). In public data analysis, M2BPGi\u2010related fibrosis and glycolysis\u2010related signatures were positively correlated with a mechanistic target of rapamycin complex 1 (mTORC1)\u2010related anabolic signature (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.439 and\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.670, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and a high mTORC1\u2010related signature was associated with worse OS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0074).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Preoperative M2BPGi identifies fibrosis\u2010related risk after HCC resection, whereas tumor metabolic activity further distinguishes patients with particularly poor outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ags3.70272","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:38:38Z","timestamp":1788248318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mac\u20102 Binding Protein Glycosylation Isomer (\n                    <scp>M2BPGi<\/scp>\n                    )\u2013Based Risk Stratification Refined by Tumor Metabolic Activity in Hepatocellular Carcinoma"],"prefix":"10.1002","author":[{"given":"Kojiro","family":"Shirabe","sequence":"first","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Mita","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-2520","authenticated-orcid":false,"given":"Shinji","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-8288","authenticated-orcid":false,"given":"Takeo","family":"Toshima","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8589-0038","authenticated-orcid":false,"given":"Norifumi","family":"Iseda","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Isoda","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousei","family":"Ishigami","sequence":"additional","affiliation":[{"name":"Department of Clinical Radiology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4497-1816","authenticated-orcid":false,"given":"Tomoharu","family":"Yoshizumi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/s41575-025-01143-y","article-title":"Improving Surgical Treatments for Hepatocellular Carcinoma","volume":"23","author":"Malik A. K.","year":"2026","journal-title":"Nature Reviews. 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C.","year":"2025","journal-title":"Liver Cancer"},{"key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/hep4.1715","article-title":"Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation","volume":"5","author":"Itoh S.","year":"2021","journal-title":"Hepatol Commun"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhepr.2026.101901","article-title":"Prognostic Significance of Pretreatment (18)F\u2010FDG PET\/CT in Hepatocellular Carcinoma: A Systematic Review and Meta\u2010Analysis","volume":"8","author":"Min J. H.","year":"2026","journal-title":"JHEP Rep"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1245\/s10434-014-3686-6","article-title":"Effect of Body Composition on Outcomes After Hepatic Resection for Hepatocellular Carcinoma","volume":"21","author":"Itoh S.","year":"2014","journal-title":"Annals of Surgical Oncology"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101309","article-title":"Hepatic mTORC1 Signaling Activates ATF4 as Part of Its Metabolic Response to Feeding and Insulin","volume":"53","author":"Byles V.","year":"2021","journal-title":"Molecular Metabolism"},{"key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00535-017-1425-z","article-title":"Mac\u20102 Binding Protein Glycan Isomer (M2BPGi) is a New Serum Biomarker for Assessing Liver Fibrosis: More Than a Biomarker of Liver Fibrosis","volume":"53","author":"Shirabe K.","year":"2018","journal-title":"Journal of Gastroenterology"},{"key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1111\/hepr.13648","article-title":"Hepatic Stellate Cell as a Mac\u20102\u2010Binding Protein\u2010Producing Cell in Patients With Liver Fibrosis","volume":"51","author":"Gantumur D.","year":"2021","journal-title":"Hepatology Research"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single Cell RNA Sequencing of Human Liver Reveals Distinct Intrahepatic Macrophage Populations","volume":"9","author":"MacParland S. A.","year":"2018","journal-title":"Nature Communications"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00259-019-04638-4","article-title":"Hypoxia\u2010Induced Modulation of Glucose Transporter Expression Impacts (18)F\u2010Fluorodeoxyglucose PET\u2010CT Imaging in Hepatocellular Carcinoma","volume":"47","author":"Xia H.","year":"2020","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/jso.26982","article-title":"Application of Albumin\u2010Bilirubin Grade and Platelet Count to Indocyanine Green\u2010Based Criteria for Hepatectomy: Predicting Impaired Liver Function and Postoperative Outcomes of Hepatocellular Carcinoma","volume":"126","author":"Takamoto T.","year":"2022","journal-title":"Journal of Surgical Oncology"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/liv.12907","article-title":"Serum WFA+ \u2010M2BP Levels as a Prognostic Factor in Patients With Early Hepatocellular Carcinoma Undergoing Curative Resection","volume":"36","author":"Toyoda H.","year":"2016","journal-title":"Liver International"},{"key":"e_1_2_13_19_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.21873\/anticanres.15479","article-title":"Mac\u20102 Binding Protein Glycosylation Isomer as a Prognostic Marker for Hepatocellular Carcinoma With Sustained Virological Response","volume":"42","author":"Harimoto N.","year":"2022","journal-title":"Anticancer Research"},{"key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.hpb.2018.10.007","article-title":"18F\u2010FDG PET\/CT Predicts Microvascular Invasion and Early Recurrence After Liver Resection for Hepatocellular Carcinoma: A Prospective Observational Study","volume":"21","author":"Lim C.","year":"2019","journal-title":"HPB: The Official Journal of the International Hepato Pancreato Biliary Association"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/hepr.70116","article-title":"Dual Escape From Disulfidptosis and Ferroptosis Drives Highly Aggressive, Hypermetabolic Hepatocellular Carcinoma","volume":"56","author":"Mita J.","year":"2026","journal-title":"Hepatology Research"},{"key":"e_1_2_13_22_1","first-page":"36","article-title":"The Impact of TP53\u2010Induced Glycolysis and Apoptosis Regulator on Prognosis in Hepatocellular Carcinoma: Association With Tumor Microenvironment and Ferroptosis","volume":"14","author":"Toshida K.","year":"2025","journal-title":"Liver Cancer"},{"key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.jhep.2024.01.018","article-title":"Navigating the Landscape of Liver Cancer Management: Study Designs in Clinical Trials and Clinical Practice","volume":"80","author":"Cabibbo G.","year":"2024","journal-title":"Journal of Hepatology"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/s41416-020-0971-y","article-title":"Mac\u20102\u2010Binding Protein Glycan Isomer Enhances the Aggressiveness of Hepatocellular Carcinoma by Activating mTOR Signaling","volume":"123","author":"Dolgormaa G.","year":"2020","journal-title":"British Journal of Cancer"},{"key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1158\/1078-0432.CCR-21-3208","article-title":"PET\u2010Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma","volume":"28","author":"An J.","year":"2022","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_13_26_1","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/s42255-022-00616-7","article-title":"Long Non\u2010Coding RNA SNHG6 Couples Cholesterol Sensing With mTORC1 Activation in Hepatocellular Carcinoma","volume":"4","author":"Liu F.","year":"2022","journal-title":"Nature Metabolism"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.surg.2024.02.006","article-title":"Risk Factors, Patterns, and Outcome Predictors of Late Recurrence in Patients With Hepatocellular Carcinoma After Curative Resection: A Large Cohort Study With Long\u2010Term Follow\u2010Up Results","volume":"176","author":"Hsiao C. Y.","year":"2024","journal-title":"Surgery"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/ags3.70138","article-title":"Association Between Liver Function Grade and Post\u2010Hepatectomy Liver Failure in Patients With Hepatocellular Carcinoma: A Latent Class Analysis","volume":"10","author":"Liu L.","year":"2026","journal-title":"Ann Gastroenterol Surg"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ags3.70263"}],"container-title":["Annals of Gastroenterological Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ags3.70272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ags3.70272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ags3.70272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:38:41Z","timestamp":1788248321000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ags3.70272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":28,"alternative-id":["10.1002\/ags3.70272"],"URL":"https:\/\/doi.org\/10.1002\/ags3.70272","archive":["Portico"],"relation":{},"ISSN":["2475-0328","2475-0328"],"issn-type":[{"value":"2475-0328","type":"print"},{"value":"2475-0328","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ags3.70272"}}