Purpose and experimental design: 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.