{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:55:38Z","timestamp":1776081338522,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972663"],"award-info":[{"award-number":["81972663"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Colorectal cancer (CRC) remains a leading cause of cancer\u2010related deaths worldwide. Although treatment strategies for solid tumours have been revolutionized by immunotherapy, only a small subset of CRC patients benefit. Using two\u2010independent cohorts, we found the common frequently mutated genes <jats:italic>TTN<\/jats:italic> and <jats:italic>OBSCN<\/jats:italic> had the significant correlation with higher tumour mutation burden (TMB) and favourable overall survival. <jats:italic>TTN<\/jats:italic> and <jats:italic>OBSCN<\/jats:italic> also displayed significant commutation phenomenon. Therefore, based on the status of <jats:italic>TTN<\/jats:italic> and <jats:italic>OBSCN<\/jats:italic>, we stratified patients into \u2018Double\u2010WT\u2019 phenotype, \u2018Single\u2010Hit\u2019 phenotype and \u2018Double\u2010Hit\u2019 phenotype. Importantly, the \u2018Double\u2010Hit\u2019 phenotype had favourable prognosis, low malignant events propensity, and highest TMB, immune cells infiltration abundance, <jats:italic>POLE<\/jats:italic> mutation rate, microsatellite instability ratio, as well as immune checkpoints expression compared with the other two phenotypes. These results indicated that the \u2018Double\u2010Hit\u2019 phenotype suggested \u2018immune\u2010hot\u2019 tumours and potentially better immunotherapeutic efficacy. Bioinformatic algorithm assessment of immunotherapy responses also confirmed this conclusion, and the \u2018Double\u2010Hit\u2019 phenotype was found to be a better predictor of immunotherapy than <jats:italic>PD\u2010L1<\/jats:italic>, <jats:italic>PD\u20101<\/jats:italic>, <jats:italic>CTLA\u20104<\/jats:italic>, TMB and microsatellite status. This study revealed CRC patients with TTN\/OBSCN \u2018Double\u2010Hit\u2019 was significantly associated favourable prognosis, \u2018immune\u2010hot\u2019 subtype and potentially better immunotherapeutic efficacy.<\/jats:p>","DOI":"10.1111\/jcmm.16393","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T05:48:33Z","timestamp":1614145713000},"page":"3239-3251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["TTN\/OBSCN \u2018Double\u2010Hit\u2019 predicts favourable prognosis, \u2018immune\u2010hot\u2019 subtype and potentially better immunotherapeutic efficacy in colorectal cancer"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-742X","authenticated-orcid":false,"given":"Zaoqu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 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