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PTEN, RASSF1andDAPKsite-specific hypermethylation and outcome in surgically treated stage I and II nonsmall cell lung cancer patients

PTEN, RASSF1andDAPKsite-specific hypermethylation and outcome in surgically treated stage I and II nonsmall cell lung cancer patients

Authors :
Carter J. Barger
Lela Buckingham
Philip Bonomi
L. Penfield Faber
John S. Coon
Michael J. Liptay
Sanjib Basu
Anthony W. Kim
Kelly Walters
Mary J. Fidler
Source :
International Journal of Cancer.
Publication Year :
2010
Publisher :
Wiley, 2010.

Abstract

The primary objective of this study is to identify prognostic site-specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter. Paraffin-embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation. Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing. Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated. Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p = 0.006 and p = 0.029, respectively). Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p = 0.020). In univariate analysis, hypermethylation of RASSF1 at CpG sites −53 and −48 and PTEN at CpG site −1310 were the significantly associated with shorter TTR (p = 0.002 and p < 0.000, respectively). Hypermethylation of PTEN at −1310 and DAPK at −1482 were most significantly associated with outcome in multivariate analysis. These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC.

Details

ISSN :
10970215 and 00207136
Database :
OpenAIRE
Journal :
International Journal of Cancer
Accession number :
edsair.doi.dedup.....134c4fffacdc41087660e2f5e8af09ad
Full Text :
https://doi.org/10.1002/ijc.24896