Effect of RAS mutations and related immune characteristics on the prognosis of patients with MSI-H/dMMR colorectal cancer.

Abstract

Purpose: Microsatellite high instability/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) has an active tumor microenvironment, rendering it more sensitive to immune checkpoint inhibitors. Given that studies involving patients with MSI-H colorectal cancer with RAS mutations are scarce, we explored the effect of RAS mutations on the TME in patients with MSI-H/dMMR cancer and identified potential prognostic factors.

Methods: Seventy-five patients diagnosed with MSI-H/dMMR colorectal cancer were retrospectively enrolled and divided into RAS-mutant and -wild-type groups. The expression levels of CD11c⁺ dendritic cells, CD4⁺ T cells, CD8⁺ T cells, and regulatory T cell (Treg) markers were detected, and prognostic factors were analyzed.

Results: RAS-mutant MSI-H colorectal patients were more likely to have: (1) higher platelet values; (2) shorter disease-free survival (DFS); (3) lower infiltrated numbers of CD11c⁺ dendritic cells, CD4⁺ T lymphocytes, and CD8⁺ T lymphocytes, and higher infiltrated numbers of Foxp3⁺ Treg cells. In MSI-H/dMMR CRC patients: (1) the high CD11c + , CD4 +,  and CD8 +  cells infiltration group had longer DFS than the low-infiltration group, and Foxp3 + cells infiltration was not significantly correlated with DFS; (2) the RAS mutation status, number of CD11c⁺ cells infiltrated, and carbohydrate antigen 19-9 (CA19-9) level were the potential prognostic factors.

Conclusion: RAS mutations in patients with MSI-H/dMMR CRC may reduce the infiltration of CD11c⁺ dendritic cells, CD4⁺ T cells, and CD8⁺ T cells, and increase the infiltration of Foxp3⁺ Treg cells to affect the tumor microenvironment of patients. RAS gene status, CD11c + cells infiltration, and CA19-9 level were potential prognostic factors for MSI-H/dMMR CRC.