Immune-related gene-based model predicts the survival of colorectal carcinoma and reflected various biological statuses.

ABSTRACT

Bakcground Prognosis of colorectal cancer (CRC) varies due to complex genetic-microenviromental interactions, and multiple gene-based prognostic models have been highlighted. Material and Method: In this work, the immune-related genes' expression-based model was developed and the scores of each sample were calculated. The correlation between the model and clinical information, immune infiltration, drug response and biological pathways were analyzed. Results: The high-score samples have a significantly longer survival (overall survival and progression-free survival) period than those with a low score, which was validated across seven datasets containing 1,325 samples (GSE17536 (N = 115), GSE17537 (N = 55), GSE33113 (N = 90), GSE37892 (N = 130), GSE38832 (N = 74), GSE39582 (N = 481), and TCGA (N = 380)). The score is significantly associated with clinical indicators, including age and stage, and further associated with PD-1/PD-L1 gene expression. Furthermore, high-score samples have significantly higher APC and a lower MUC5B mutation rate. The high-score samples show more immune infiltration (including CD4+ and CD8+ T cells, M1/M2 macrophages, and NK cells). Enriched pathway analyses showed that cancer-related pathways, including immune-related pathways, were significantly activated in high-score samples and that some drugs have significantly lower IC50 values than those with low score. Conclusion: The model developed based on immune-related genes is robust and reflected various statuses of CRC and may be a potential clinical indicator.