{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:54:25Z","timestamp":1788274465283,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study aims to explore the genetic characteristics of biliary tract cancer (BTC), with a particular focus on the impact of DNA damage response and repair (DDR) genes on clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 180 patients with BTC and next\u2010generation sequencing data were retrospectively analyzed. Clinical outcomes were compared between DDR\u2010positive and DDR\u2010negative groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DDR mutations were found in 28.3% of patients, with ATM (7.8%), BAP1 (5.6%), and BRCA2 (3.3%) being the most common. DDR\u2010positive patients receiving first\u2010line platinum\u2010based chemotherapy (<jats:italic>n<\/jats:italic>\u00a0=\u00a073) had a signi\ufb01cantly higher objective response rate (50.0% vs. 14.9 %; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.001), longer median progression\u2010free survival (mPFS) (7.7 vs. 3.8 months; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.001) and longer median overall survival (28.6 vs. 11.9 months; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). Multivariate analysis confirmed that deleterious DDR gene mutations were independently associated with prolonged mPFS (hazard ratio [HR], 0.37; 95% CI, 0.20\u20130.67; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) and median overall survival (mOS) (HR, 0.19; 95% CI, 0.08\u20130.46; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). In 56 patients receiving immunotherapy combined with chemotherapy, DDR\u2010positive patients had a signi\ufb01cantly higher overall response rate (45% vs. 8.3%; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.001), longer mPFS (7.7 vs. 3.8 months; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.009), and longer mOS (12.7 vs. 8.8 months; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.011). Multivariate analysis showed that the presence of deleterious DDR gene mutations was associated with significantly longer mPFS (HR, 0.34; 95% CI, 0.16\u20130.73); <jats:italic>p<\/jats:italic>\u00a0=\u00a0.005] and mOS (HR, 0.23; 95% CI, 0.08\u20130.62; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Deleterious DDR gene mutations are associated with improved clinical outcomes in patients with BTC treated with platinum\u2010based chemotherapy or immunotherapy combined with chemotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35726","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:07:28Z","timestamp":1738109248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["DNA damage response and repair gene mutations predict clinical outcomes in biliary tract cancer"],"prefix":"10.1002","volume":"131","author":[{"given":"Sirui","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-5751","authenticated-orcid":false,"given":"Cheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-6773","authenticated-orcid":false,"given":"Hongfeng","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"},{"name":"Gastric Cancer Center West China Hospital Sichuan University  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102407\u20102\u201010"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14095"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102004\u2010828889"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658\u2010200110000\u201000010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0908721"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1802357"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(18)32409\u20107"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010018\u20100777\u20104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2022.40.4_suppl.378"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)00727\u20104"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/po.17.00286"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010018\u20100114\u2010z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7344"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1706450"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1903387"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(16)30559\u20109"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.cd\u201017\u20100226"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.75.7740"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201019\u20103529"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005327\u2010w"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359211070643"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010017\u20100591\u20104"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2015.4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.002"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56539"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.07.022"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.05.004"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201016\u20102520"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae125"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103630"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001317\u20107"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.35726","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:56:36Z","timestamp":1760302596000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.35726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/cncr.35726"],"URL":"https:\/\/doi.org\/10.1002\/cncr.35726","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"assertion":[{"value":"2024-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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