|
KMID : 0982820040030020077
|
|
Journal of Lung Cancer
2004 Volume.3 No. 2 p.77 ~ p.85
|
|
|
Correlation between Aberrant Promoter Hypermethylation of CpG Islands and the Clinical Outcome of Non-small Cell Lung Cancer after Curative Resection
|
|
Lee Seung-Hee
Kim Young-Tae
Sung Sook-Whan
Kim Joo-Hyun
|
|
|
Abstract
|
|
|
Purpose: Aberrant methylation of CpG islands has been suggested as one of the cause for development of cancer by forcing specific tumor suppressor gene function. The methylation status of primary non-small cell lung cancer (NSCLC) was investigated and its clinical relevance was tested whether it could predict the clinical outcomes after curative resection.
Materials and Methods: We analyzed 61 tissue samples from NSCLC patients using methylation-specific PCR (MSP) and searched for promoter hypermethylation of the genes p16INK4a, retinoic acid receptor β2 promoter (RARβ P2), 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 p16INK4a, 49% (30 of 61) for RARβ P2, 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 RARβ P2 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 RARβ P2 (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 RARβ 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.
|
|
|
KEYWORD
|
|
|
Gene, Molecular biology, Non-small cell lung cancer, Polymer chain reaction, Prognosis
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|