Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers

Abstract

To determine the aberrant methylation status of RASSF1A,p16 and DAPK gene promoter region in induced sputum from lung cancer patients and the value of their combined detection in diagnosing lung cancers. Methylation-specific PCR (MSP) was used to detect the promoter methylation status of RASSF1A, p16, and DAPK genes in induced sputum and pathological tissues from 82 patients with lung cancers and 25 patients with pulmonary benign lesion. We also analyzed the relation between methylation status and clinical pathological data. The positive rates of promoter methylation of RASSF1A, p16, and DAPK genes in pathological tissues from patients with lung cancers were 63.4%, 59.8%, and 58.5%, respectively,and those in induced sputum were 54.9%, 48.8%, and 51.2%, respectively. The promoter methylation of RASSF1A,p16, and DAPK genes were not detected in patients with pulmonary benign lesion. There was a significant difference between the lung cancer group and pulmonary benign lesion group (P<0.05). The methylation rate of RASSF1A gene was significantly lower in the middle and high differentiation and non-metastastic lymph node of lung cancer tissues than that in the poor differentiation and the metastatic lymph node of lung cancer tissues(P<0.05), and was not correlated with age, sex, smoking index, clinical stage, and pathological types.The methylation rate of p16, and DAPK genes was not significantly correlated with all the above mentioned factors (P>0.05). The methylation rate of joint detecting RASSF1A, p16, and DAPK genes was 73.2%. Joint detection for promoter hypermethylation of RASSF1A, p16, and DAPK genes in induced sputum may be used as a simple and effective index of the diagnosis and prognose of lung cancers, and can improve the positive rate.