DNA glycosylase (NEIL3) overexpression associated with low tumor immune infiltration and poor overall patient survival in endometrial cancer

Endometrial cancer (EC) is the most common gynecological malignancy. Although prognosis is favorable for patients with an early-stage disease, those with recurrent or more advanced disease have low response rates to chemotherapy and poor clinical outcomes. Previously, we have shown that DNA repair gene (NEIL3) is required for retaining replication fork integrity during replication stress. Here, we examined whether the overexpression of NEIL3 in endometrial cancer associated with altered genomic instability, tumor immunogenicity and anti-tumor immunity in endometrial tumor. In this study, we show that endometrial cancer patients with tumors that a have high NEIL3 expression associated with worse overall survival (OS) outcomes in patients. In addition, tumor with high NEIL3 expression is associated with high number of mutation and chromosomal instability. Furthermore, NEIL3 expression in EC tumors positively correlated with mutation of DNA polymerase eta (POLE) and TP53 as well as high expression of replicative polymerases genes (POLE, POLD1 and POLA1). In contrast, tumor with high NEIL3 expression exhibit low tumor immunogenicity and poor anti-tumor immune cell infiltration. Our findings may have important clinical implications for utilizing NEIL3 as a potential prognostic biomarker to stratify EC patients and as a target to enhance immunotherapy response in endometrial cancer. However, our NEIL3 overexpression associated observation still requires further experimental-based scientific validation studies.