Detection of aberrant promoter methylation of GSTP1 in the tumor and serum of Chinese human primary hepatocellular carcinoma patients.
OBJECTIVE
Glutathione S-transferases, enzymes that prevent cells from damage mediated by oxidant and electrophilic carcinogens, may be early critical determinants of carcinogenesis. To explore the aberrant promoter CpG island methylation of the GSTP1 gene as a biomarker for screening hepatocellular carcinoma (HCC) high risk individuals and for the early detection of HCC, we analyzed its methylation in the tumor and non-tumor tissues and serum samples from 26 patients with HCC, as well as serum from 8 liver cirrhosis patients by methylation-specific PCR (MSP).


RESULTS
Twenty-three of 26 (88.5%) tumor tissues and 18 of 26 (69%) corresponding non-tumor tissues displayed GSTP1 promoter CpG island hypermethylation. Similarly, GSTP1 promoter hypermethylation was detected for the first time in 16 of 32 (50%) of circulating tumor DNA in the peripheral serum from HCC patients and 4 of 8 (50%) cirrhosis tissues and 3 of 8 (37.5%) corresponding serum DNA from cirrhosis patients. The aberrant methylation of the GSTP1 gene in the serum of patients is in agreement with tumor methylation status (P = 0.004). None of the 12 normal PBMC samples were methylation positive.


CONCLUSIONS
These data indicate that the epigenetic aberrance of promoter CpG island hypermethylation of the GSTP1 gene may contribute to the hepatopathogenesis of HCC and is a potential valuable biomarker for noninvasive disease monitoring and HCC early diagnosis.
Wang
Jinhong
J
Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, People's Republic of China.
Qin
Yang
Y
Li
Bo
B
Sun
Zhilin
Z
Yang
Bo
B
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D051549:Glutathione S-Transferase pi / Q000097:blood / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic
C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi