title: Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma (HCC).
  
  
  METHODS
  Sixty-eight patients with HCC (mean age of 69.1 ± 10.1), 31 cirrhosis patients (mean age of 59.3 ± 6.3) and 33 healthy volunteers (mean age of 51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein (AFP) values with HCC clinicopathological features, such as tumor size, number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion (diameters; ≤ 3 cm, 3-5 cm and ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer (BCLC) criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alpha-fetoprotein levels were kept at -80 °C until use. Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.
  
  
  RESULTS
  In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number, presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls (P < 0.001). Prolidase levels were significantly associated with tumor size and number (P < 0.001, P = 0.002, respectively). Prolidase levels also differed in patients in terms of BCLC staging classification (P < 0.001). Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis (P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately (P = 0.032, P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation (r = 0.616; P < 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification, whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.
  
  
  CONCLUSIONS
  Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Sevil Uygun
authors.initials: SU
authors.lastname: Ilikhan
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Muammer
authors.initials: M
authors.lastname: Bilici
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Sahin
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Ayşe Semra Demir
authors.initials: AS
authors.lastname: Akca
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Can
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Ibrahim Ilker
authors.initials: II
authors.lastname: Oz
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Berrak
authors.initials: B
authors.lastname: Guven
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: M Cagatay
authors.initials: MC
authors.lastname: Buyukuysal
authors.affiliation: Sevil Uygun Ilikhan, Muammer Bilici, Hatice Sahin, Department of Internal medicine, Bülent Ecevit University Faculty of Medicine, Zonguldak 67100, Turkey.
authors.forename: Yucel
authors.initials: Y
authors.lastname: Ustundag
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D004150:Dipeptidases / Q000097:blood*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D047368:Tumor Burden; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: C097353:AFP protein, human; D000509:alpha-Fetoproteins; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase
keywords: Alpha-fetoprotein; Cirrhosis; Hepatocellular carcinoma; Macrovascular invasion; Prolidase