AKR1B10 expression is associated with less aggressive hepatocellular carcinoma: a clinicopathological study of 168 cases

Schmitz, Klaus; Sotiropoulos, Georgios C.; Baba, Hideo A.; Schmid, Kurt Werner; Müller, Doris; Paul, Andreas; Auer, T.; Gamerith, Gabriele; Löffler‐Ragg, Judith

doi:10.1111/j.1478-3231.2011.02511.x

Cited by 52 publications

(73 citation statements)

References 25 publications

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“…High AKR1B10 expression was significantly associated with lower AJCC T-stage and lower BCLC stage, which was consistent with previous reports 14,26. High AKR1B10 expression was correlated with no early recurrence, but not with the late recurrence.…”

Section: Discussionsupporting

confidence: 92%

High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

Song

Lee

et al. 2014

Gut Liver

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Background/AimsUpregulation of aldo-keto reductase 1B10 (AKR1B10) through the mitogenic activator protein-1 signaling pathway might promote hepatocarcinogenesis and tumor progression. The goal of this study was to evaluate the prognostic significance of AKR1B10 protein expression in patients with hepatocellular carcinoma after surgery.MethodsA tissue microarray was used to detect the expression level of AKR1B10 protein in tumors from 255 patients with hepatocellular carcinoma who underwent curative hepatectomy. The impact of AKR1B10 expression on the survival of patients was analyzed. The median follow-up period was 119.8 months.ResultsHigh AKR1B10 protein expression was observed in 125 of the 255 patients with hepatocellular carcinoma (49.0%). High AKR1B10 expression was significantly associated with a lack of invasion of the major portal vein (p=0.022), a lack of intrahepatic metastasis (p=0.010), lower the American Joint Committee on Cancer T stage (p=0.016), lower the Barcelona Clinic Liver Cancer stage (p=0.006), and lower α-fetoprotein levels (p=0.020). High AKR1B10 expression was also correlated with a lack of early recurrence (p=0.022). Multivariate analyses of survival revealed that intrahepatic metastases and lower albumin levels were independent predictors of both shorter recurrence-free survival and shorter disease-specific survival. High AKR1B10 expression was an independent predictor of both longer recurrence-free survival (p=0.024) and longer disease-specific survival (p=0.046).ConclusionsHigh AKR1B10 protein expression might be useful as a marker of a favorable prognosis in patients with hepatocellular carcinoma after curative hepatectomy.

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Section: Discussionsupporting

confidence: 92%

High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

Song

Lee

et al. 2014

Gut Liver

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“…Other studies found that HCCs with low AKR1B10 levels were highly proliferative, poorly differentiated and had a poor prognosis (23,24). In agreement with these studies, the present study identified that AKR1B10 mRNA levels were elevated in HCCs, and that prognosis (RFS and OS) was worse in cases in which the amounts of AKR1B10 mRNA were lower in HCC tissue than in CN tissue.…”

Section: Discussionsupporting

confidence: 81%

“…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.…”

Section: Discussionmentioning

confidence: 85%

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

et al. 2016

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Abstract. When assessing outcome in hepatocellular carcinoma (HCC), it is important to consider prognostic factors in background non-tumorous liver tissue as well as in the tumor, since multiple occurrence is associated with background liver status such as hepatitis. The current study aimed to elucidate molecular prognostic predictors that have an association with HCC background non-tumorous tissue. Microarray expression profiling identified aldo-keto reductase family 1, member B10 (AKR1B10) as a putative non-tumorous prognostic factor, and AKR1B10 gene expression was investigated in 158 curatively resected HCC cases by reverse transcription-quantitative polymerase chain reaction. AKR1B10 expression (AKR1B10 value/GAPDH value x 1,000) was significantly higher in tumor tissue (median, 9.2200; range, 0.0003-611.0200; n=158) than in the corresponding non-tumorous tissue (median, 0.5461; range, 0.0018-69.0300; n=158) (P<0.001). When the samples were grouped according to AKR1B10 expression in tumor tissue relative to non-tumorous tissue, tumor

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“…AKR1B10 is expressed at very low levels in normal lung, breast, and pancreatic tissues (27), whereas ectopic overexpression of AKR1B10 has been reported in lung small cell cancers, breast cancers, pancreatic cancers, liver cancers, and cervical cancers (28)(29)(30)(31)(32). These inconsistent results indicate that AKR1B10 likely has different roles in different types of cancers; in particular, we speculate that AKR1B10 has an inhibitory effect on colorectal carcinogenesis and progression, whereas its function may be favorable for other cancers.…”

Section: Discussionmentioning

confidence: 83%

AKR1B10, a Transcriptional Target of p53, Is Downregulated in Colorectal Cancers Associated with Poor Prognosis

Ohashi

Idogawa

Sasaki

et al. 2013

Molecular Cancer Research

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p53 is one of the most important tumor suppressor genes, and it is frequently inactivated in various cancers. p53 modulates various cellular functions, such as apoptosis and cell-cycle arrest via transcriptional regulation. Recently, p53 has been reported to be involved in a wide range of cellular metabolic pathways, including glycolysis, oxidative phosphorylation, glutaminolysis, and the antioxidant response. To understand the functional mechanism of p53, it is important to find out the direct transcriptional targets of p53. In this study, aldo-keto reductase family 1, member B10 (AKR1B10) was identified as a direct target of the p53 family by cDNA microarray analysis after comparing the mRNA expression of control and H1299 cells that overexpressed with p53 family members. In addition, we found that the expression of AKR1B10 was significantly decreased in colorectal cancers and adenomas as compared with normal colon tissues. Knockdown of AKR1B10 significantly inhibited p53-induced apoptosis in colorectal cancer cells, whereas the overexpression of AKR1B10 enhanced p53-induced apoptosis and inhibited tumor proliferation in vivo. Furthermore, low expression of AKR1B10 in colon cancer patients was correlated with decreased survival and poor prognosis. These results suggest that decreased expression of AKR1B10 could disrupt the tumor suppressive function of p53, which result in decreased survival in colorectal cancer patients. In summary, AKR1B10 may be a novel prognostic predictor and a novel therapeutic target for colorectal cancer.

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AKR1B10 expression is associated with less aggressive hepatocellular carcinoma: a clinicopathological study of 168 cases

Cited by 52 publications

References 25 publications

High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

High Expression of Aldo-Keto Reductase 1B10 Is an Independent Predictor of Favorable Prognosis in Patients with Hepatocellular Carcinoma

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

AKR1B10, a Transcriptional Target of p53, Is Downregulated in Colorectal Cancers Associated with Poor Prognosis

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