Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6999
Peer-review started: October 27, 2014
First decision: November 14, 2014
Revised: December 3, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: June 14, 2015
AIM: 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.
CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.
Core tip: Prolidase cleaves dipeptide bonds containing proline, playing a vital role in collagen turnover, matrix remodeling and cell growth. Neoplastic transformation results in deregulation of tissue collagen metabolism, in which metastatic tumor cells produce enhanced amounts of proteases to penetrate basement membranes and the extracellular matrix. Therefore, tumor progression might depend on the breakdown of collagen and other extracellular matrix proteins. The role of prolidase in neoplastic tissues is unknown. Herein, serum prolidase levels in hepatocellular carcinoma (HCC) patients were significantly associated with tumor size and number, Barcelona-clinic liver cancer staging and α-fetoprotein (AFP). Considering the levels of both serum prolidase and AFP could contribute to early diagnosis of HCC.