Prognostic value of apoptosis-associated speck-like protein containing a CARD gene promoter methylation in resectable non-small-cell lung cancer.

摘要

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). PATIENTS AND 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 promoterhypermethylation 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). CONCLUSION: 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.