AKR1C1-3, notably AKR1C3, are distinct biomarkers for liver cancer diagnosis and prognosis: Database mining in malignancies

Aldo-keto reductases, known as AKR1C1-AKR1C4 enzymes, are pivotal to NADPH-dependent reduction, and their expression is highly associated with the progression of malignant cancers. However, the expression and distinct prognostic value of the AKR1C family members in liver cancer are not well established. In the current study, the expression of AKR1C isoforms was studied using the Oncomine online databases. In addition, their expression profiles were analyzed in cancer cell lines using data from the Cancer Cell lines Encyclopedia (CCLE) database. Furthermore, the mRNA expression levels of AKR1C family members between liver cancer and normal liver samples were assessed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The AKR1C1-3 prognostic value was further investigated by the Kaplan-Meier plotter database in liver cancer patients. It was found that the expression levels of AKR1C3 were elevated significantly in liver cancer tissues and cells as demonstrated by the Oncomine, CCLE and GEPIA databases. The expression levels of AKR1C1 and AKR1C2 in liver cancer tissues did not increase significantly in the Oncomine database while expression was significantly high in CCLE and GEPIA databases. However, the expression levels of the AKR1C4 gene as determined by the CCLE, GEPIA and Oncomine databases were not consistent. Therefore, the Kaplan-Meier survival curves of liver cancer patients with the expression of AKR1C1-3 genes were next analyzed. The data indicated that high expression levels of AKR1C1-3 were correlated with lower overall survival in liver cancer patients. Using the co-expression and PPI network, AKR1C1-3 genes were identified that were involved in the same pathway displaying 44 total unique interactors. These results suggested that the increased AKR1C1-3, notably AKR1C3 expression levels served as possible diagnostic biomarkers and essential prognostic factors for liver cancer patients. The roles of AKR1C4 in liver cancer require further examination.