{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:38:34Z","timestamp":1747147114960,"version":"3.40.5"},"reference-count":48,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":9,"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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Therapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB \u226510 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores \u226510 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score \u22650.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR\u2009=\u20090.16; 95% CI: 0.056\u20130.46, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), as well as patients with both TMB \u22653.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score \u22650.36.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6441","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:29:39Z","timestamp":1697081379000},"page":"20470-20481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune checkpoint inhibitor\u2010related molecular markers predict prognosis in extrahepatic cholangiocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7488-8204","authenticated-orcid":false,"given":"Bao","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoluhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1036-3369","authenticated-orcid":false,"given":"Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-0527","authenticated-orcid":false,"given":"Xinting","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenze","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-4223","authenticated-orcid":false,"given":"Yilei","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Beidou Precision Medicine Institute  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Wang","sequence":"additional","affiliation":[{"name":"Beidou Precision Medicine Institute  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhirong","family":"Qian","sequence":"additional","affiliation":[{"name":"Beidou Precision Medicine Institute  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-4643","authenticated-orcid":false,"given":"Yingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-3259","authenticated-orcid":false,"given":"Shunda","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences&amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30915-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0245"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30157-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30109-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/hbsn.2019.08.05"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-203394"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1105"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3507"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo.2018.08.18"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02745-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.0930"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00856"},{"key":"e_1_2_10_17_1","first-page":"476","article-title":"Alignment of high\u2010throughput sequencing data inside in\u2010memory databases","volume":"205","author":"Firnkorn D","year":"2014","journal-title":"Stud Health Technol Inform"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016489.2018.1552015"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3294-x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw520"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-4-r41"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2234-y"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt755"},{"key":"e_1_2_10_24_1","first-page":"PO.17.00084","article-title":"Reliable pan\u2010cancer microsatellite instability assessment by using targeted next\u2010generation sequencing data","volume":"1","author":"Middha S","year":"2017","journal-title":"JCO precis Oncologia"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.1.321"},{"key":"e_1_2_10_26_1","first-page":"PO.17.00011","article-title":"OncoKB: a precision oncology Knowledge Base. 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