title: Expression of thioredoxins and glutaredoxins in human hepatocellular carcinoma: correlation to cell proliferation, tumor size and metabolic syndrome.
abstract: Thioredoxins (Trx) and glutaredoxins (Grx) are thiol oxidoreductases that are ubiquitously expressed, and are involved in several biological processes. The expression of thioredoxins and glutaredoxins is induced in many neoplasms, and correlates with prognosis in gallbladder and colorectal carcinoma. The aim of the present study was to examine the expression pattern of these proteins (redoxins) in hepatocellular carcinoma (HCC) and to correlate their levels with clinical features. Paraffin-embedded tissues from 25 patients resected for HCC and 15 patients resected for colorectal carcinoma (CRC) liver metastases were analyzed with immunohistochemistry. Our results showed that Trx1, Trx2 and Grx5 were upregulated in HCCs as compared to the respective surrounding liver. In comparison, almost all redoxins were upregulated in CRC liver metastases, with Trx1 and Grx3 being significantly more increased in the CRC liver metastases than in the primary HCC tumors. In HCC, Trx1 correlated significantly with cell proliferation, and with a trend towards increased levels with micro-vascular invasion, while expression of Trx2 decreased with tumor size. Trx1 levels were lower in tumors of males, smokers, and patients with high alcohol consumption. Grx2 levels were significantly higher in patients with metabolic syndrome. In conclusion, this study illustrates specific correlations of individual redoxins to clinical features of HCC, and implicates the redoxins in the pathogenesis of HCC.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Mollbrink
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Jawad
authors.affiliation: Department of Chemistry, University of Patras, Rion, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Vlamis-Gardikas
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Edenvik
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Isaksson
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Danielsson
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Stål
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: A P
authors.initials: AP
authors.lastname: Fernandes
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D054477:Glutaredoxins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000032:analysis; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D013879:Thioredoxins / Q000032:analysis* / Q000235:genetics; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C516008:GLRX2 protein, human; C404105:GLRX3 protein, human; C516011:GLRX5 protein, human; D054477:Glutaredoxins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C491203:TXN protein, human; C467002:TXN2 protein, human; D013879:Thioredoxins