Clinical and Biological Significances of AKR1B1 in Gastric Carcinoma

Objectives AKR1B1 is aberrantly expressed in various tumours, including gastric carcinoma (GC), but its biological role and clinical prognostic value in GC are still unclear. This study aimed to explore the intrinsic association between AKR1B1 and gastric cancer based on the analysis and experimental validation of the public dataset of gastric cancer.Methods The expression level of AKR1B1 and its relationship with the clinical pathologic characteristics of GC were analyzed. Cox regression was used to analyze the relationship between clinicopathological features and overall survival (OS) of gastric cancer, and Kaplan-Meier curves and nomograms were plotted for prognostic analysis. CIBERSORT and Tumor Immune Estimation Resource (TIMER) website tools were used to investigate the effect of AKR1B1 with the level of immune cell infiltration in gastric cancer and its cumulative survival. Gene Set Enrichment Analysis (GSEA) was used to analyze the main biological functions of AKR1B1 in gastric cancer. In addition, immunohistochemistry and RT-qPCR were used to validate the clinical samples of gastric cancer patients.Results Public dataset analysis showed that the high expression of AKR1B1 in gastric cancer tissues was significantly associated with poor overall survival (OS) prognosis. Cox analysis showed that elevated AKR1B1 expression, age, and initial treatment outcome were independent risk factors for OS, and a prognostic nomogram with high diagnostic efficacy could be established. The expression level of AKR1B1 was positively correlated with the number of dendritic cells (DCs) and M2 macrophages infiltrating in gastric cancer. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways related to the high-expression phenotype of gastric cancer AKR1B1 include the intestinal immune network of IgA antibody production, the interaction of cytokines and their receptors, the adhesion of cell matrix involved in focal adhesions, the cytokine signaling pathway, the cell adhesion molecular pathway, and the interaction between the extracellular matrix and its receptors. Experimental verification showed that the expression of AKR1B1 was up-regulated in gastric cancer tissues.Conclusions The above results suggest that AKR1B1 is involved in the biological process of gastric cancer and is closely related to its prognosis, and may be a valuable indicator molecule.