The pan-cancer landscape of aldo-keto reductase1B10 reveals that its expression is diminished in gastric cancer

Introduction: Aldo-keto reductase 1B10 (AKR1B10) is a multifunctional enzyme, which is important in cancer development and progression, but the landscape of AKR1B10 in pan-cancers and in tumor microenvironment is unclear.

Method: This study integrated the sequencing data of 33 cancer types, including gastric cancer, from TCGA project to explored the expression pattern and genetic and epigenetic alterations of AKR1B10. The association of AKR1B10 expression with clinical progression of cancers was evaluated by Kaplan-Meier analysis; the potential role of AKR1B10 in tumor microenvironment (TME) and immune-related gene expression were analyzed by PURITY, ESTIMATE, TIMER and CIBERSORT algorithms. The expression of AKR1B10 and immune cell markers in gastric cancer were evaluated with multiplex immunofluorescence staining.

Result: Results indicated that AKR1B10 was highly expressed in the gastrointestinal tract in health donors, but the expression of AKR1B10 was significantly changed in most of cancer types, which may be ascribed to DNA methylation in its promoter. The AKR1B10 expression in cancers and its value in disease progression was bidirectional and functionally enriched in metabolism in pan-cancers. In tumor microenvironment, AKR1B10 was significantly correlated with immune cell infiltrations and immune gene expression. In the stomach, along with the diminishing of AKR1B10 expression, CD68+ macrophage increased and CD19+ B cell decreased in gastric cancer.

Discussion: These data indicates that AKR1B10 may be an important factor in the development and progression and a potential therapeutic target for multiple cancers, but plays as a protector in the gastric tissues.