mutations benefit colorectal cancer patients receiving immune checkpoint inhibitors.

Background: Colorectal cancer (CRC) is a malignant tumor associated with a high mortality rate. While the advent of immune checkpoint inhibitors (ICIs) has been a gamechanger, only a small percentage of CRC patients benefit from ICIs. The pathological mechanism of CRC is not well understood, but somatic mutations, especially missense mutations, are believed to play an important role. This study examined the relationship between ICIs in colorectal cancer and missense mutations in the axonemal dynein heavy chain gene 7 ().

Methods: A clinical cohort (n=690) and the CRC data from the publicly available Cancer Genome Atlas (TCGA) were examined. Gene Set Enrichment Analysis, ESTIMATE analysis, and clinical correlation analysis were performed to explore the effects and mechanisms of mutation on immunotherapy in colorectal cancer.

Results: The results showed that CRC patients with mutations can benefit more from ICIs (P<0.05). Patients with mutation had higher ESTIMATE scores, immune scores, and matrix scores, compared to patients without the mutation (P<0.001). The transport of small molecules, keratinization, asthma, autoimmune thyroid disease, allograft rejection, and other pathways were significantly enriched in mutated tissues (P<0.05). The top key genes associated with the mutation included AQP8, MS4A12, GUCA2B, and ZG16 (P<0.01).

Conclusions: The current study not only demonstrated the significance of as a risk factor and prognostic feature in CRC, but also revealed that mutations might affect the clinical efficacy of ICIs by impacting the tumor immune microenvironment.