Document Detail

Can aberrant promoter hypermethylation of CpG islands predict the clinical outcome of non-small cell lung cancer after curative resection?
MedLine Citation:
PMID:  15797047     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Aberrant methylation of CpG islands acquired in tumor cells in promoter regions is one cause for the loss of gene function. We examined whether aberrant DNA hypermethylation could be used to predict the clinical outcomes of patients with primary nonsmall cell lung cancer (NSCLC) after curative resection. METHODS: We tested 61 patients with NSCLC using methylation-specific polymerase chain reaction (MSP) and searched for promoter hypermethylation of the genes p16INK4a, retinoic acid receptor beta-promoter (RARbetaP2), death-associated protein kinase (DAPK), and O6-methylguanine-DNA-methyltransferase (MGMT). The clinical data, the presence of DNA hypermethylation, and clinical outcomes were analyzed. RESULTS: Hypermethylation in the tumor samples was detected in 67% (41 of 61) for p16(INK4a), 49% (30 of 61) for RARbetaP2, 30% (18 of 61) for DAPK, and 62% (38 of 61) for MGMT. Thirty patients (49%) developed recurrence within 33 months; 16 in the remaining lung, 10 in other organs, and 4 in both. We found no correlation between the specific DNA hypermethylation and any of the clinicopathological characteristics of the patients. DNA hypermethylation was not associated with a different survival or recurrence rate. However, the aberrant hypermethylation of RARbetaP2 seemed to be related to the location of cancer recurrence. Although advanced T stage and preoperative chemotherapy were statistically significant in univariate analysis, unmethylation of DAPK (p = 0.030) and hypermethylation of RARbetaP2 (p = 0.014), as well as advanced T stage (p = 0.075) and preoperative chemotherapy (p = 0.025), were significant risk factors in multivariate analysis for early recurrence in the remaining lung. CONCLUSIONS: The P2 hypermethylation of the RARbeta gene and unmethylation of DAPK seem to be important factors in predicting early cancer recurrence in the remaining lung and could be used as a prognostic marker in NSCLC. However, the clinical implications of this finding need further investigation.
Young Tae Kim; Seung Hee Lee; Sook Whan Sung; Joo Hyun Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  79     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-30     Completed Date:  2006-08-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1180-8; discussion 1180-8     Citation Subset:  AIM; IM    
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Cancer Research Institute, Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.
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MeSH Terms
Apoptosis Regulatory Proteins
Calcium-Calmodulin-Dependent Protein Kinases / genetics
Carcinoma, Non-Small-Cell Lung / genetics,  pathology,  surgery*
Combined Modality Therapy
CpG Islands*
DNA Methylation*
Lung Neoplasms / genetics,  surgery*
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
O(6)-Methylguanine-DNA Methyltransferase / genetics
Promoter Regions, Genetic*
Receptors, Retinoic Acid / genetics
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Receptors, Retinoic Acid; 0/retinoic acid receptor beta; EC Methyltransferase; EC protein kinase; EC Protein Kinases

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