ArticleJournal of cellular and molecular medicine2021
TTN/OBSCN 'Double-Hit' predicts favourable prognosis, 'immune-hot' subtype and potentially better immunotherapeutic efficacy in colorectal cancer.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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53 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
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Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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