Abstract
Introduction: While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease. Annual low-dose computed tomography screening decreases lung cancer mortality, however effective biomarkers to address the high false positive rate and to better define high risk individuals are lacking. This study was designed to identify potential DNA methylation markers for the detection of non-small cell lung cancer, the most common type of lung cancer. Methods: 152 candidate methylation genes were first investigated in lung cancer cell lines and a pilot set of lung tissues. Five promising methylated genes, DMRTA, HOXA9, ZIC4, HOXA7, and SIX3, were selected and further validated in 150 non-small cell lung cancers and 142 tumor-free surrounding lung tissues using the quantitative methylation-specific PCR. Results: Methylation levels of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 were significantly higher in tumors compared to tumor-free surrounding lung tissues (P 0.05). Conclusion: We identified a group of highly sensitive and specific methylation markers in non-small cell lung cancer. These markers are potential valuable candidates to improve the performance of lung cancer screening.
Highlights
While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease
Selection of methylation markers with lung cancer cell lines and tissue samples Methylation status of 152 candidate genes was assessed in four lung cancer cell lines with methylation-specific PCR (MSP) (Supplemental Table 3)
Methylation levels of the 33 genes were further quantified in the pilot set of 26 tissue samples with quantitative real-time methylationspecific PCR (qMSP)
Summary
While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease. In the United States, more than 221,000 new cases of lung cancer will be diagnosed in 2015, and over 158,000 individuals will die of this disease. This account for 26.8% of total deaths caused by all cancers [2]. While the survival of patients diagnosed with SCLC is almost universally poor, surgical resection can be curative in patients with early-stage NSCLC [4,5]. In the absence of effective early detection, the majority of NSCLC patients are diagnosed with advanced-stage disease
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