Expression of methylation-related genes is associated with overall survival in patients with non-small cell lung cancer

• Published in: British journal of cancer Vol. 98; no. 10; pp. 1716 - 1722
• Main Authors: Xing, J, Stewart, D J, Gu, J, Lu, C, Spitz, M R, Wu, X
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.05.2008; Nature Publishing Group
• Subjects: Adult; Aged; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - mortality; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methylation; DNA Methyltransferase 3B; DNA, Neoplasm - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Resistance; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Genetics and Genomics; Humans; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; Molecular Medicine; Multivariate Analysis; Oncology; Pneumology; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Proportional Hazards Models; RNA, Messenger - metabolism; Survival Analysis; Texas - epidemiology; Tumors; Tumors of the respiratory system and mediastinum; non-small cell lung cancer; DNA methyltransferase; prognosis; hypermethylation; Human; Lung disease; Prognosis; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Gene expression; Survival; Cancerology; non-small cell lung cancer prognosis; Bronchus disease; Methylation; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604343

The abnormality of DNA methylation is involved in tumour progression, and thus has a modulating effect on clinical outcome of cancer patients. In this study, we measured the mRNA expression levels of three methylation-regulating genes ( DNMT1 , DNMT3b , and MBD2 ) in 148 tumour samples from patients with non-small cell lung cancer (NSCLC) using quantitative real-time polymerase chain reaction and then determined their prognostic values. Our data showed that the high level of DNMT1 expression was significantly associated with an increased risk of death in all NSCLC patients (hazard ratio (HR), 1.74; 95% confidence interval (95% CI), 1.04–2.90). However, the high level of DNMT3b expression was significantly associated with poor prognosis only in young patients (<65 years). The high level of MBD2 expression had a significantly reduced risk for death only in male patients and in squamous cell lung carcinoma (SQLC) patients. All three combination groups with DNMT1 and DNMT3b , DNMT1 and MBD2 or DNMT3b and MBD2 revealed significant combined effects in male patients and SQLC patients. Our results suggest that DNMT1, DNMT3b, and MBD2 may play important roles in modulating NSCLC patient survival and thus be useful for identifying NSCLC patients who would benefit most from aggressive therapy.