title: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. htudura@juntendo.ac.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsuzura
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. genda@rice.ocn.ne.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Genda
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. syusato@juntendo.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. perseverance3@hotmail.co.jp.
authors.forename: Ayato
authors.initials: A
authors.lastname: Murata
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. yoshio-k.s52@live.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. ynarita@juntendo.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Narita
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. s-ogawa@juntendo.ac.jp.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. klinsmann1011@yahoo.co.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. ten2617@gmail.com.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. khirano-tym@umin.ac.jp.
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. katsu0716@shore.ne.jp.
authors.forename: Katsuyori
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pathology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. mdksmrwjunten522@ybb.ne.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Wada
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. takafumi@air.ocn.ne.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D053673:Glypicans / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006521:Hepatitis, Chronic / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
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