title: Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas.
abstract: The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase-like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor-associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumor-associated protein variants that represent members of the aldo-keto reductase (AKR) superfamily. Human aldose reductase-like protein-1 (hARLP-1) was the most prominent tumor-associated AKR member detected in HCC by 2-dimensional electrophoresis (2-DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms (hARLP-1, 36/7.4 (kd/pI); hARLP-2, 36/7.2; hARLP-3, 36/6.4; and hARLP-4, 33/7.35). In addition, a human aldose reductase-like protein (hARLP-5, 36/7.6) was identified that differed from hARLP-1 by 1 amino acid (D313N), indicating 2 allelic forms of the human aldose reductase-like gene. A novel antibody directed against common parts of the hARLPs revealed hARLP reactivity in human HCC by immunohistochemistry. Furthermore, aldose reductase (AR) was identified and characterized as a tumor-associated variant. In conclusion, in all investigated human HCCs at least one of the various types of the described tumor-associated proteins of the AKR superfamily was clearly present. Of these HCC samples, 95% were positive for hARLPs as proven by 2-DE analysis and/or by use of the antibody directed against hARLP. Thus, hARLP is a strong candidate for use as an immunohistochemical diagnostic marker of human HCC.
authors.affiliation: Institute of Pathology, Ludwig Maximilians University of Munich, Munich, Germany. Evelyn-Eberhart@lrz.uni-muenchen.de
authors.forename: Evelyn
authors.initials: E
authors.lastname: Zeindl-Eberhart
authors.forename: Sibylle
authors.initials: S
authors.lastname: Haraida
authors.forename: Sibylle
authors.initials: S
authors.lastname: Liebmann
authors.forename: Peter Roman
authors.initials: PR
authors.lastname: Jungblut
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lamer
authors.forename: Doris
authors.initials: D
authors.lastname: Mayer
authors.forename: Gundula
authors.initials: G
authors.lastname: Jäger
authors.forename: Stephen
authors.initials: S
authors.lastname: Chung
authors.forename: Hartmut Manfred
authors.initials: HM
authors.lastname: Rabes
mesh_terms: D000328:Adult; D000429:Alcohol Oxidoreductases / Q000032:analysis / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010449:Peptide Mapping; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase