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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
- 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.
- Subjects :
- Male
Cancer Research
Lung Neoplasms
Tumor suppressor gene
Immunoenzyme Techniques
Antigens, CD
Carcinoma, Non-Small-Cell Lung
medicine
Humans
PTEN
Promoter Regions, Genetic
Lung cancer
DNA Modification Methylases
Lung
Cyclin-Dependent Kinase Inhibitor p16
In Situ Hybridization, Fluorescence
Adaptor Proteins, Signal Transducing
Aged
Monomeric GTP-Binding Proteins
Neoplasm Staging
biology
Tumor Suppressor Proteins
PTEN Phosphohydrolase
Cancer
Methylation
DNA Methylation
Middle Aged
Cadherins
Prognosis
medicine.disease
Neoplasm Proteins
Survival Rate
Death-Associated Protein Kinases
DNA Repair Enzymes
Treatment Outcome
Oncology
CpG site
Case-Control Studies
Calcium-Calmodulin-Dependent Protein Kinases
DNA methylation
biology.protein
Cancer research
Adenocarcinoma
CpG Islands
Female
Neoplasm Recurrence, Local
Apoptosis Regulatory Proteins
Follow-Up Studies
Subjects
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