High expression of the ferroptosis-associated MGST1 gene in relation to poor outcome and maladjusted immune cell infiltration in uterine corpus endometrial carcinoma.

Abstract

BackgroundUterine corpus endometrial carcinoma (UCEC) tightly correlates with dysregulated iron homeostasis. MGST1 (microsomal glutathione S‐transferase 1) involves in the regulation of oxidative stress and plays a key role in inhibiting iron‐mediated cell death in cancer cells. Hence, we aimed to illuminate the characteristics of MGST1 expression and prognosis in UCEC using bioinformatics prediction to provide novel perspectives for theoretical supplementation and ferroptosis‐based immunotherapy.MethodsWe retrieved MGST1 expression data via several public data portals. The relationships between MGST1 expression and clinicopathologic characteristics as well as survival time were evaluated via multivariate methods and Kaplan–Meier survival curves. The MGST1‐interacting protein–protein interaction was also established by the STRING website. The TIMER and GEPIA databases were used to illustrate the association between MGST1 expression and infiltrated immune cells. We used the MethSurv website and the UALCAN website to determine the relationship between MGST1 expression and DNA methylation.ResultsMGST1 overexpression in UCEC compared with normal tissues correlates with different histological types, a lack of hormone therapy and poor survival time. MGST1 interacts with several ferroptosis‐related proteins. Overexpression of MGST1 was accompanied by lower levels of NK cell and CD8+ T cell infiltration, higher myeloid‐derived suppressor cell infiltration and different immunocytes with corresponding markers. Hypermethylation and low promoter methylation cooperate to regulate MGST1 expression.ConclusionElevated MGST1 expression is related to tumour development and poor prognosis, as well as dysregulated infiltration of immune cells in UCEC, which can be a potential prognostic indicator and ferroptosis‐based immunotherapy target.