title: Aldoketoreductase family 1B10 (AKR1B10) as a biomarker to distinguish hepatocellular carcinoma from benign liver lesions.
abstract: Hepatocellular carcinoma (HCC) is one of the most common highly aggressive malignant tumors worldwide. Aldoketoreductase 1B10 (AKR1B10) was first isolated from HCC and further identified to be over-expressed in many cancers from various organs. AKR1B10 contributes to detoxification of xenobiotics by lipid peroxidation and metabolizes physiological substrates such as farnesal, retinal, and carbonyls. Metabolizing these lipid substrates plays a crucial role in promoting carcinogenesis. In the present study, immunohistochemical analysis was performed to determine the prevalence/pattern of AKR1B10 expression in HCC and its usefulness to differentiate benign liver lesions from HCC. Oncogenic function of AKR1B10 was examined in hepatocellular carcinoma cells in vitro using Western blotting and shRNA knockdown approaches, with emphasis on cell apoptosis and response to chemotherapy. Immunohistochemistry analysis revealed AKR1B10 was overexpressed in 97% (86/89) of hepatocellular carcinomas, with minimal to no expression in adjacent hepatic tissue, while hepatic adenomas and focal nodular hyperplasia did not exhibit expression of AKR1B10. shRNA-mediated silencing of AKR1B10 expression in hepatocellular carcinoma cells resulted in (1) increased cell apoptosis, (2) decreased colony formation and size, and (3) enhanced cytoreductive response following exposure to doxorubicin chemotherapy. Our findings provide first time evidence that AKR1B10 is a unique biomarker involved in hepatocellular carcinogenesis via modulation of proliferation, cell apoptosis and chemoresistance and is a potential promising biomarker to differentiate HCCs from benign hepatic lesions.
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Matkowskyj
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Han
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Wanying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Haonan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Sambasiva
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Reed
authors.initials: R
authors.lastname: Omary
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: g-yang@northwestern.edu.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000032:analysis* / Q000096:biosynthesis; D000074408:Aldo-Keto Reductases; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000175:diagnosis*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: AKR1B10; Focal nodular hyperplasia; Hepatic adenoma; Hepatocellular carcinoma