Open AccessTTN/OBSCN ‘Double‐Hit’ predicts favourable prognosis, ‘immune‐hot’ subtype and potentially better immunotherapeutic efficacy in colorectal cancer
Author(s) -
Liu Zaoqu,
Wang Libo,
Guo Chunguang,
Liu Long,
Jiao Dechao,
Sun Zhenqiang,
Wu Kunpeng,
Zhao Yanan,
Han Xinwei
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16393
Subject(s) - microsatellite instability , immunotherapy , colorectal cancer , phenotype , immune system , oncology , medicine , cancer , cancer research , dna mismatch repair , immunology , biology , gene , microsatellite , genetics , allele
Colorectal cancer (CRC) remains a leading cause of cancer‐related deaths worldwide. Although treatment strategies for solid tumours have been revolutionized by immunotherapy, only a small subset of CRC patients benefit. Using two‐independent cohorts, we found the common frequently mutated genes TTN and OBSCN had the significant correlation with higher tumour mutation burden (TMB) and favourable overall survival. TTN and OBSCN also displayed significant commutation phenomenon. Therefore, based on the status of TTN and OBSCN , we stratified patients into ‘Double‐WT’ phenotype, ‘Single‐Hit’ phenotype and ‘Double‐Hit’ phenotype. Importantly, the ‘Double‐Hit’ phenotype had favourable prognosis, low malignant events propensity, and highest TMB, immune cells infiltration abundance, POLE mutation rate, microsatellite instability ratio, as well as immune checkpoints expression compared with the other two phenotypes. These results indicated that the ‘Double‐Hit’ phenotype suggested ‘immune‐hot’ tumours and potentially better immunotherapeutic efficacy. Bioinformatic algorithm assessment of immunotherapy responses also confirmed this conclusion, and the ‘Double‐Hit’ phenotype was found to be a better predictor of immunotherapy than PD‐L1 , PD‐1 , CTLA‐4 , TMB and microsatellite status. This study revealed CRC patients with TTN/OBSCN ‘Double‐Hit’ was significantly associated favourable prognosis, ‘immune‐hot’ subtype and potentially better immunotherapeutic efficacy.