{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:29:44Z","timestamp":1783542584451,"version":"3.55.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Given the high postoperative recurrence rates and poor prognosis of cholangiocarcinoma (CCA), this study aimed to evaluate cytochrome C oxidase subunit 6B2 (COX6B2) as a potential biomarker for recurrence prediction and to develop a composite risk stratification model integrating clinicopathologic features for personalized treatment planning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We first performed an unbiased recurrence-oriented transcriptomic screening using TCGA-CHOL and GSE107943 data sets. Recurrence-upregulated genes were subjected to log-rank survival testing, univariate Cox regression, and cross-cohort intersection to identify candidate recurrence-associated genes. COX6B2 was then evaluated at the protein level by immunohistochemistry in a training cohort (N = 115) and an independent validation cohort (N = 48). A composite recurrence risk stratification model incorporating COX6B2 and routine clinicopathologic variables, including carbohydrate antigen 19-9, carcinoembryonic antigen, vascular invasion, and tumor size, was developed and validated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Bioinformatics analysis revealed significant\n                      <jats:italic toggle=\"yes\">COX6B2<\/jats:italic>\n                      upregulation in recurrent CCA (hazard ratio, 1.351;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .034). COX6B2 alone demonstrated robust predictive performance with AUC values of 0.87 (training cohort) and 0.81 (validation cohort). The composite model achieved superior predictive accuracy (AUC, 0.93) and effectively stratified patients into high-risk (5-year recurrence rate: 90.62%-95.59%) and low-risk (recurrence-free rate: 85.11%-87.50%) groups. The model's negative predictive value improved by 11% compared with COX6B2 alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>COX6B2 may serve as a clinically useful tissue-based biomarker for postoperative recurrence prediction in CCA. By integrating COX6B2 with standard clinicopathologic features, the composite model provides a practical approach for recurrence risk assessment and individualized postoperative management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00349","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:59:12Z","timestamp":1783540752000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Development and Validation of a Cytochrome C Oxidase Subunit 6B2\u2013Based Risk Model for Cholangiocarcinoma Recurrence"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9659-8881","authenticated-orcid":true,"given":"Meiru","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, China"},{"name":"Department of Gastroenterology, Hengshui People's Hospital, Hengshui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-0231","authenticated-orcid":true,"given":"Xiaoli","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hengshui People's Hospital, Hengshui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hengshui People's Hospital, Hengshui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hengshui People's Hospital, Hengshui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8308-2287","authenticated-orcid":true,"given":"Dongqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.21037\/hbsn-20-396"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091216"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-022-11463-x"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000517992"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000005977"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2018172889"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14020392"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-020-02053-w"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-3059"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-020-0231-2"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58108"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.12.031"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.04.038"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.11.302"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-026-04592-2"},{"key":"e_1_3_6_17_2","doi-asserted-by":"crossref","unstructured":"Zhou Z Wang P Sun R et al: Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3. J Immunother Cancer 9:e001946 2021","DOI":"10.1136\/jitc-2020-001946"},{"key":"e_1_3_6_18_2","doi-asserted-by":"crossref","unstructured":"Zhou S-L Zhou Z-J Hu Z-Q et al: Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence. J Hepatol 71:1152-1163 2019","DOI":"10.1016\/j.jhep.2019.07.014"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001946"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.07.014"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28404-y"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0740-4"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-45056-9"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.9178"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.03.019"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102355"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201223RR"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.02.027"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-26-00349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:59:18Z","timestamp":1783540758000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-26-00349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1200\/PO-26-00349"],"URL":"https:\/\/doi.org\/10.1200\/po-26-00349","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2600349"}}