Detection of HOXA9 gene methylation in tumor tissues and induced sputum samples from primary lung cancer patients

Background: Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening modality exists for lung cancer. We aimed to evaluate the prevalence of HOXA9 promoter methylation in tissue and induced sputum samples from Korean patients with lung cancer. Methods: Using pyrosequencing, HOXA9 methylation was analyzed for 40 pairs of primary lung cancer and normal tissues and 185 induced sputum specimens, including 76 patients with lung cancer. Results: The methylation of HOXA9 in lung cancer tissue was significantly higher compared with normal tissues (67.4%+/- 17.6% vs. 23.6%+/- 10.3%, respectively; p < 0.001). With a cut-off of > 45.6% of HOXA9 gene methylation in tissues, the sensitivity was 90.5% and the specificity was 97.5%. In induced sputum specimens, the HOXA9 gene in lung cancer patients was significantly more hypermethylated compared with patients with benign lung diseases and the healthy group (23.4%+/- 15.9%, 14.9%+/- 7.9%, and 9.7%+/- 5.0%, respectively; p < 0.001). Conclusions: The HOXA9 gene was hypermethylated in 32 of 40 tumors (80%), especially in early stages of lung cancer. HOXA9 methylation could be a potential biomarker to aid early detection and prognosis.