Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis

Abstract

Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs), similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover, the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered preneoplastic conditions for HCC, has not been fully elucidated. The aim of this study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC tissue samples compared to corresponding non-tumorous liver tissues (NTs), comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the significance of molecular changes at the preneoplastic stages of HCC. Immunohistochemical analysis demonstrated that the median expression levels of AKR1B10 were higher in HCCs than in NTs (p < 0.001) and higher in NTs than NLs (p < 0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs, respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs and NLs with no significant difference between expression in NTs and NLs. Furthermore, a multivariate analysis identified an association between hepatic steatosis and AKR1B10 expression in NTs (p = 0.020). Of the three protein expressed in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic conditions, and a steatosis-related factor might influence its expression.

Apoptotic Effect of Combination of Epalrestat and Palmitic Acid in Cholangiocarcinoma RBE Cells

“…Consistent with previous findings [1][2][3], we found that ARK1B10 is over expressed in various liver cancer cells like HepG2, BEL-7402, and PLC; however, cholangiocarcinoma RBE cells displayed more AKR1B10 protein than any of the liver cancer cells listed above. The questions of whether or not it existed in cholangiocarcinoma tissue sample and the clinical significance of ARK1B10 over-expression in cholangiocarcinoma are not answered in this study.…”

“…The expression of AKR1B10, detected by Immunohistochemical analysis, is highest in HCC, then in non-tumorous liver tissues, and lowest in normal liver tissues with 54.8%, 2.1%, and 0.3% positive expression, respectively [3].…”

“…Over expression of this gene occurs in various cancer cells [2], especially in liver cancer, but its expression is minimal in normal liver cells [3]. AKR1B10 expression is mostly observed in the small intestine and colon, but a low amount of its mRNA exists in the liver [1].…”

Prognostic significance of AKR1B10 gene expression in hepatocellular carcinoma and surrounding non-tumorous liver tissue

“…As shown by Zhang et al (22), AKR1B10 promotes pancreatic carcinogenesis via modulation of the K-RAS/E-cadherin pathway. Several studies demonstrated AKR1B10 expression in HCC via immunohistochemistry (23)(24)(25)(26). To the best of our knowledge, however, there are no reports comparing AKR1B10 expression in HCC and CN tissue or determining its association with HCC prognosis.…”

The homeobox NKX and Neoplasms in Digestive system: a systematic review.

“…While the function of NKX6.1 in gastrointestinal tumors, like HCC, have increasingly become the focus of attention in recent years. HCC is the fifth most common cancer and the third leading cause of cancer-related death worldwide [67][68][69] . The incidence of HCC has increased over serval years, but unfortunately, the long-term survival of HCC patients are still not ideal.…”