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

Abstract

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<non-tumorous expression (n=26) significantly correlated with poor recurrence-free survival (P=0.0074) and overall survival (OS) (P<0.0001), and was an independent prognostic factor for OS (P=0.0011) in a multivariate analysis. The ratio of AKR1B10 messenger RNA levels in HCC and corresponding non-tumorous tissues may predict prognosis after curative hepatectomy, with low expression in HCC tissue relative to non-tumorous tissue indicative of poor prognosis. IntroductionHepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related mortality worldwide (1). Although hepatectomy is one of the most effective options for HCC without distant metastases (2-4), 80% of HCC patients experience intrahepatic recurrence even after curative resection, and 50% die within 5 years (5). The types of intrahepatic recurrence are mainly divided into two types: Intrahepatic metastasis (IM), which involves the development of HCC foci from primary tumor cells and their spread to the remnant liver via the portal vein before or during hepatectomy; and multicentric occurrence (MO), which involves the development of new HCC foci due to chronic active hepatitis or cirrhosis provoked by viruses, alcohol, toxins or other HCC risk factors (6-9). In other words, when the clinicopathological factors for HCC recurrence are divided into two categories such as tumor factors and background liver factors, IM tends to be related to tumor factors and MO is rather related to background liver factors, since IM reflects the characteristics of the primary tumor and MO exhibits different genetic features from the primary lesions.The clinical progression and outcomes of IM and MO differ significantly, as determined by several studies (8-10). Therefore, distinguishing between these conditions is important for designing therapeutic strategies and predicting prognosis. Usually, the pattern of HCC intrahepatic recurrence is determined histologically, but it is sometimes diffi...

A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

“…A prevalent serum marker would improve clinical management of HCC. Secretory AKR1B10 protein is overexpressed in HCC, (14,25) and studies on surgical specimens and clinicopathological data indicated its potential as a marker for early-stage HCC, (32,33) prognosis, (27,34,35) BLT discrimination, (26) and stratification of HCC risk in liver hepatitis B virus and hepatitis C virus infections. (36)(37)(38)(39) These studies of AKR1B10 in HCC pave the road for this large-scale multicenter serological study for detection of HCC, including early-stage HCC and AFP-negative HCC.…”

Prognostic significance of AKR1B10 in patients with resected lung adenocarcinoma

“…Sonohara et al . reported that the ratio of AKR1B10 messenger RNA levels in HCC and corresponding non‐tumorous tissues may predict prognosis after curative hepatectomy, with low expression in HCC tissue relative to non‐tumorous tissue indicative of poor prognosis . Yoshitake et al .…”

“…The AKR1B10 gene encodes a member of the AKR superfamily . Human AKR1B10 is reported to be overexpressed in several human cancers, including lung and liver cancers . AKR1B10 is often overexpressed in male and smoking NSCLC patients, therefore AKR1B10 has been proposed as a diagnostic marker in smokers with NSCLC .…”

Prognostic value of aldo-keto reductase family 1 member B10 in solid tumors: a systematic review and meta-analysis

“…After full-text review, 12 articles were excluded. Eventually, we identi ed 11 articles published between 2014 and 2019, which were included in the nal analysis [5][6][7][8][9][10][11][12][13][14][15]. The ow diagram of the literature search is shown in Fig1.…”

“…Studies have shown that AKR1B10 is characterized by obvious carcinogenicity and can be used as a tumor marker [4]. Recently, an increasing number of studies showed that abnormal expression of AKR1B10 is signi cantly correlated with the prognosis of certain solid tumors [5][6][7][8][9][10][11][12][13][14][15]. However, the currently available results are inconsistent, and the prognostic value of AKR1B10 remains unclear.…”