The Oncologist, 2025, Vol, XX, Issue XX Predictive role of ARID1A and B2M mutations and the antigen presentation pathway in the efficacy of definitive chemoradiotherapy for cervical cancer.

BACKGROUND AND PURPOSE: Definitive chemoradiotherapy (dCRT) is the standard treatment for locally advanced cervical cancer (LACC), yet patients experience considerable variability in disease-free survival (DFS). This study aimed to identify molecular biomarkers associated with response to dCRT in cervical cancer.Materials and methods: We retrospectively analyzed targeted next-generation sequencing data from tumor biopsy samples of 31 patients diagnosed with FIGO stage IIB-IVA LACC. Genetic alterations in cancer-related genes and pathways were assessed to determine associations with DFS. Immune cell infiltration and gene expression were analyzed using data from The Cancer Genome Atlas. RESULTS: Genetic alterations were frequently detected in PIK3CA (45.2%), EP300 (25.8%), RB1 (19.4%), FBXW7 (19.4%), and FAT1 (16.1%). Multivariate analysis identified mutations in ARID1A and B2M as independent predictors of poor DFS. Alterations in the antigen processing and presentation pathway were also associated with reduced survival rates. Patients with ARID1A and B2M mutations exhibited decreased immune cell infiltration and impaired antigen presentation, indicating a compromised immune response. CONCLUSION: ARID1A and B2M mutations may serve as potential biomarkers for predicting treatment outcomes in cervical cancer patients undergoing dCRT. Testing for these mutations could help identify patients at higher risk of poor outcomes, guiding personalized treatment strategies to improve survival rates.