Introduction:Immunotherapy benefits gastrointestinal tumor patients. But traditional biomarkers like TMB and MSI can’t precisely identify beneficiaries. Phosphatidylinositol - 3,4,5 - triphosphate - dependent Rac exchange factor 2 (PREX2) plays a complex role in tumorigenesis.
Methods:In a retrospective study of 1764 patients (1385 colorectal, 379 gastric), NGS of 639 genes and PD - L1 staining were done.
Results:In colorectal cancer, PREX2 mutations were associated with increased TMB, MSI, TMB-H, and MSI-H. Mechanistically, this is related to an increased number of tumor pathway mutations, higher PD - L1 expression, increased immune infiltration, and immune - related pathway enrichment. Cetuximab and Bortezomib sensitivity was higher in PREX2 - mutated colorectal cancer. In gastric cancer, there are no established immune associations with PREX2 mutations.
Conclusion:PREX2 mutations may serve as a novel predictive biomarker for immunotherapy in CRC, potentially enhancing antitumor immunity via microenvironment modulation, but lack predictive value in GC. These findings highlight PREX2's role in refining patient stratification for immune checkpoint inhibitors.