Diagnostic and prognostic values of AKR1C3 and AKR1D1 in hepatocellular carcinoma
Male
0301 basic medicine
0303 health sciences
Carcinoma, Hepatocellular
Liver Neoplasms
Aldo-Keto Reductase Family 1 Member C3
Down-Regulation
Hep G2 Cells
Middle Aged
Prognosis
3. Good health
03 medical and health sciences
Gene Ontology
Area Under Curve
Case-Control Studies
Cell Line, Tumor
Gene Knockdown Techniques
Humans
Female
Protein Interaction Maps
RNA, Messenger
Oxidoreductases
Research Paper
Cell Proliferation
Proportional Hazards Models
DOI:
10.18632/aging.202380
Publication Date:
2021-01-22T15:24:48Z
AUTHORS (7)
ABSTRACT
Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer and the majority of patients are diagnosed at an advanced stage and have a poor prognosis. AKR1C3 (Aldo-keto reductase family 1 member C3) and AKR1D1 (Aldo-keto reductase family 1 member D1) catalyze the conversion of aldehydes and ketones to alcohols and play crucial roles in multiple cancers. However, the functions of AKR1C3 and AKR1D1 in HCC remain unclear. In our study, data from the public databases were selected as training and validation sets, then 76 HCC patients in our center were chosen as a test set. Bioinformatics methods suggested AKR1C3 was overexpressed in HCC and AKR1D1 was down-regulated. The receiver operating characteristic curve (ROC) analysis was performed and the area under curve (AUC) values of AKR1C3 and AKR1D1 were above 0.7 (0.948, 0.836, respectively). Also, the high expression of AKR1C3 and low expression of AKR1D1 predicted poor prognosis and short median survival time. Then, the knockdown of AKR1C3 and overexpression of AKR1D1 in HCC cells were achieved with lentivirus. And both decreased cell proliferation, restrained cell viability, and inhibited tumorigenesis. Moreover, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted and the results showed that AKR1C3 and AKR1D1 might participate in the MAPK/ERK and androgen receptor (AR) signaling pathway. Furthermore, the AR and phosphorylated ERK1/2 were significantly reduced after the suppression of AKR1C3 or overexpression of AKR1D1. Collectively, AKR1C3 and AKR1D1 might serve as candidate diagnostic and prognostic biomarkers for HCC and provide potential targets for HCC treatment.
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CITATIONS (19)
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