Browse

Can aberrant promoter hypermethylation of CpG islands predict the clinical outcome of non-small cell lung cancer after curative resection?

Cited 30 time in Web of Science Cited 32 time in Scopus
Authors
Kim, Young Tae; Lee, Seung Hee; Sung, Sook Whan; Kim, Joo Hyun
Issue Date
2005-03-31
Publisher
Elsevier
Citation
Ann Thorac Surg. 2005 Apr;79(4):1180-8; discussion 1180-8.
Keywords
AdultAgedApoptosis Regulatory ProteinsCalcium-Calmodulin-Dependent Protein Kinases/geneticsCarcinoma, Non-Small-Cell Lung/genetics/pathology/*surgeryCombined Modality Therapy*CpG Islands*DNA MethylationHumansLung Neoplasms/genetics/*surgeryMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingO(6)-Methylguanine-DNA Methyltransferase/genetics*Promoter Regions, GeneticReceptors, Retinoic Acid/genetics
Abstract
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.
ISSN
1552-6259 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15797047

https://hdl.handle.net/10371/13873
DOI
https://doi.org/10.1016/j.athoracsur.2004.09.060
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Thoracic Surgery (흉부외과학전공)Journal Papers (저널논문_흉부외과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse