Impact of the Location of CpG Methylation within the GSTP1 Gene on Its Specificity as a DNA Marker for Hepatocellular Carcinoma

摘要: Hypermethylation of the glutathione S-transferase π 1 (GSTP1) gene promoter region has been reported to be a potential biomarker distinguish hepatocellular carcinoma (HCC) from other liver diseases. However, reports regarding how specific marker it is have ranged 100% 0%. We hypothesized that, large extent, variation specificity depends on location CpG sites analyzed. To test this hypothesis, we compared methylation status GSTP1 DNA isolated HCC, cirrhosis, hepatitis, and normal tissues by bisulfite-PCR sequencing. found that 5' position -48 nt transcription start site selectively methylated in whereas 3' all examined, including HCC tissue. Interestingly, when derived fetal 11 nonhepatic tissue was also examined sequencing, appeared liver-specific. A methylation-specific PCR assay targeting developed used quantify various diseased HCC. When an region, 5'-end significantly more than 3'-end (97.1% vs. 60%, p<0.0001 Fisher's exact test) for distinguishing (n = 120) hepatitis 35) cirrhosis 35). Encouragingly, 33.8% AFP-negative contained gene. This study clearly demonstrates importance liver-specific should considered epigenetic studied detection