No association between GSTP1 gene aberrant promoter methylation and prognosis in surgically resected hepatocellular carcinoma patients from the Basque Country (Northern Spain).
OBJECTIVE
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, being linked etiologically to several factors. Glutathione-S-transferases (GSTs) are a family of enzymes that play an important role in detoxification. Hypermethylation of regulatory sequences at glutathione-S-transferase pi class gene (GSTP1) has been found in different human tumor types. In this study, we have studied the methylation status of the GSTP1 promoter region in patients from the Basque Country (Northern Spain) by methylation-specific PCR (MSP).


RESULTS
GSTP1 aberrant promoter methylation was present in 24 of 117 (20.5%) tumor samples being associated with late stages of tumor progression. Patients with multiple HCCs showed different patterns of methylation, which could suggest a different clonal origin of multicentric HCC or different degrees of differentiation. No effect on disease-free survival or overall survival was observed in patients with GSTP1 methylated who underwent curative resection.


CONCLUSIONS
We can conclude that GSTP1 promoter CpG island methylation appears to be a less common event during hepatocarcinogenesis in European populations than in Asian populations, being associated with late stages of tumor progression. These findings could also be useful to provide new therapeutic strategies through the use of demethylating agents.
Anzola
Monica
M
Departamento de Z. y Dinámica Celular, Facultad de Farmacia, Universidad del País Vasco, Paseo Universidad 7, 01006-Vitoria, Spain.
Cuevas
Nerea
N
López-Martínez
Monica
M
Saiz
Alberto
A
Burgos
Juan José
JJ
de Pancorbo
Marian Martínez
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
D004273:DNA, Neoplasm; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase