Analysis of NQO1 polymorphisms and p53 protein expression in patients with hepatocellular carcinoma
Mei-Miao Chiu1*, Ying-Ju Ko1*, Ann-Ping Tsou2, Gar-Yang Chau3 and Yat-Pang Chau1
1Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 2Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University and Department of Surgery and 3Taipei-Veterans General Hospital, Taipei, Taiwan
*Both authors contribute equally.
Offprint requests to: Yat-Pang, Chau., Ph.D., Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 155, 2nd Sec., Li-Nung Street, Shih-Pai, Taipei, Taiwan 112, Republic of China. e-mail: leonchau@ym.edu.tw
Gar-Yang, Chau, Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital-Taipei, 201 Sec. 2, Shih-Pai Road, Taipei, Taiwan 217, Republic of China. e-mail: gychau@vghtpe.gov.tw
Summary. NAD(P)H: quinone oxidoreductase 1 (NQO1), a cytosolic enzyme which catalyzes the two-electron reduction of quinone compounds, has been suggested to prevent the generation of semiquinone free radicals and reactive oxygen species, thus protecting cells from oxidative damage. However, the enzymatic activity of NQO1 strongly depends on the individual genetic polymorphism of the NQO1 gene. A common NQO1 polymorphism is a C to T transition at position 609, which results in an inactive enzyme. Recent studies showed that NQO1 is an important enzyme for stabilizing p53 protein, which is involved in anti-tumorigenesis. Thus, the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism may play a pivotal role in tumor development.
This study aimed to investigate the relationship between C609T NQO1 polymorphism and p53 expression in human hepatocellular carcinoma (HCC). Genotyping of NQO1 was performed on 100 HCC specimens by PCR-RFLP analysis. In addition, NQO1 and p53 protein expression in HCC samples at different TNM stages was determined by immunohistochemistry. Our data showed that (1) the frequency of C609T NQO1 was significantly increased in TNM stage III HCC patients; (2) no significant association was found between p53 expression and C609T polymorphism of NQO1 gene; and (3) a tumor/non-tumor (T/N) ratio > 1.27 of NQO1 expression revealed by real-time qPCR analyses was positively correlated with poorer survival in patients with tumors >5 cm, suggesting that an increase of NQO1 expression may be an indicator of advanced tumor progression. This study provides important information about NQO1 genotypes and its expression to HCC tumor development and progression. Histol Histopathol 24, 1223-1232 (2009)
Key words: Hepatocellular carcinoma, NAD(P)H, Quinone oxidoreductase 1 (NQO1), P53 gene
DOI: 10.14670/HH-24.1223