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Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Translational Research and Biomarkers

Evaluation of the Association of Urokinase Plasminogen Activator System Gene Polymorphisms with Susceptibility and Pathological Development of Hepatocellular Carcinoma

Authors: Chia-Jui Weng, PhD, Chiung-Man Tsai, MS, Yi-Chen Chen, PhD, Yi-Hsien Hsieh, PhD, Chiao-Wen Lin, MS, Yu-Fan Liu, PhD, Shih-Chi Su, MS, Mu-Kuan Chen, PhD, Shun-Fa Yang, PhD

Published in: Annals of Surgical Oncology | Issue 12/2010

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Abstract

Background

The urokinase plasminogen activator (uPA) system is a serine proteinase system involved in extracellular matrix (ECM) degradation. The levels of uPA system components in tumor tissues are implicated as prognostic biomarkers in a wide range of malignancies. Although the contributions of uPA system components to the formation of many types of cancer are well known, their possible association with the prediction of risk and prognosis of hepatocellular carcinoma (HCC) remains poorly investigated.

Methods

A total of 102 HCC patients and 344 controls were recruited. Genetic polymorphisms of uPA system genes, including uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis.

Results

When individuals were classified into male and female subgroups to estimate adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) of each uPA system gene, the HCC risks of males and females with PAI-1 5G/5G genotype were 6.06-fold (95% CI = 1.39–26.36) and 0.04-fold (95% CI = 0.003–0.69), respectively, as compared with those with PAI-1 4G/4G genotype. High risk for hepatitis B surface antigen (HBsAg)-positive clinical status and significantly higher serum aspartate aminotransferase (AST) concentration were exhibited in HCC patients with PAI-1 4G/5G and 5G/5G genotypes as compared with 4G/4G homozygotes.

Conclusions

The results suggest that PAI-1 genotypes could be an important factor contributing to increased susceptibility and pathological development of HCC in Taiwanese population.
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Metadata
Title
Evaluation of the Association of Urokinase Plasminogen Activator System Gene Polymorphisms with Susceptibility and Pathological Development of Hepatocellular Carcinoma
Authors
Chia-Jui Weng, PhD
Chiung-Man Tsai, MS
Yi-Chen Chen, PhD
Yi-Hsien Hsieh, PhD
Chiao-Wen Lin, MS
Yu-Fan Liu, PhD
Shih-Chi Su, MS
Mu-Kuan Chen, PhD
Shun-Fa Yang, PhD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1124-y

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