ATM mutations as an independent prognostic factor and potential biomarker for immune checkpoint therapy in endometrial cancer

Abstract The morbidity and mortality of endometrial cancer has been increasing over years. Ataxia telangiectasia mutated (ATM) gene, encoding a protein kinase participated in the response to DNA damage, is frequently mutated in endometrial cancer patients. However, the potential relationship between ATM mutations and the progression of endometrial cancer remains unclear. We performed an integrative bioinformatics analysis to investigate the relationship between ATM mutational status with clinical outcomes and tumor microenvironment in endometrial cancer patients. The whole exome sequencing data, RNA sequencing data and clinical information were collected from The Cancer Genome Atlas (TCGA) dataset. We found that mutation in the ATM gene was an independent prognostic factor for endometrial cancer. Antitumor immune pathways were enriched in endometrial tumors with ATM mutations. The tumor-infiltrating T lymphocytes, especially cytotoxic lymphocytes, were generally more abundant in tumors with ATM mutations. Furthermore, patients with ATM mutations exhibited higher tumor mutational burden, higher neoantigen load and increased expression levels of some immune checkpoints. In conclusion, the present study indicated that ATM mutations were linked to longer overall survival of endometrial cancer. Our findings may add better understanding for potential immunotherapy of endometrial cancer.