Prognostic value of apoptosis-associated speck-like protein containing a CARD gene promoter methylation in resectable non-small-cell lung cancer.
BACKGROUND
The apoptosis-associated speck-like protein containing a CARD (ASC) is a newly identified tumor suppressor gene that is frequently inactivated by de novo promoter methylation in non-small-cell lung cancer (NSCLC).


METHODS
We studied 79 patients with NSCLC who had undergone surgery with curative intent. The ASC promoter methylation status was determined by methylation-specific polymerase chain reaction. Statistical analyses (all 2-sided) were performed to determine the prognostic effect of hypermethylation on various clinical parameters.


RESULTS
ASC promoter hypermethylation was detectable by methylation-specific polymerase chain reaction in 9 of 70 (12.9%) normal lungs and in 33 of 70 (47.1%) matching tumor samples of patients with NSCLC. The mean ASC methylation level was significantly higher in tumor than in matching normal tissue (P < 0.001). ASC methylation in normal tissue was always accompanied with ASC methylation in matching tumor tissue. Patients without ASC promoter hypermethylation showed a significantly better survival than patients with ASC promoter hypermethylation (P = 0.007). Multivariate analysis revealed ASC promoter methylation as an independent unfavorable prognostic factor (P = 0.009).


CONCLUSIONS
Our results indicate that ASC promoter hypermethylation is a common event in patients with primary NSCLC, and this epigenetic alteration is associated with inferior survival, suggesting that ASC promoter hypermethylation might be an important biomarker for a biologic, aggressive disease in NSCLC.
Zhang
Zhixue
Z
Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
Tan
Sheng
S
Zhang
Lin
L
D000328:Adult; D000368:Aged; D053468:CARD Signaling Adaptor Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human