{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:32:35Z","timestamp":1790519555118,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Beijing Science and Technology Innovation Medical Development Foundation","award":["KC2023-JX-0186-FZ099"],"award-info":[{"award-number":["KC2023-JX-0186-FZ099"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874173"],"award-info":[{"award-number":["81874173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LY22H160019"],"award-info":[{"award-number":["LY22H160019"]}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y-MSDZD2022-0161"],"award-info":[{"award-number":["Y-MSDZD2022-0161"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these 2 mutations have exactly the same effects on tumor cells and the tumor microenvironment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 was more prominent in IDH1 mutants. IDH mutants were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication and repair cluster.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae132","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T17:23:34Z","timestamp":1717694614000},"page":"e1061-e1072","source":"Crossref","is-referenced-by-count":11,"title":["Differential isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutation-related landscape in intrahepatic cholangiocarcinoma"],"prefix":"10.1093","volume":"29","author":[{"given":"Shuaishuai","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, and Key Laboratory of Cancer Prevention and Intervention, Ministry of Education , Hangzhou , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linping","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, and Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health , Hangzhou , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital, Zhejiang 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