Seung Soo Yoo1, Su Man Lee2, Sook Kyung Do1, Won Kee Lee3, Dong Sun Kim4, Jae Yong Park5. 1. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea. 2. Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Republic of Korea. 3. Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea. 4. Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Republic of Korea. Electronic address: doskim@knu.ac.k. 5. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea. Electronic address: jaeyong@knu.ac.kr.
Abstract
OBJECTIVES: Lung cancer is the leading cause of cancer-related deaths and is currently a major health problem owing to difficulties in diagnosis at the early stage of the disease. Changes in DNA methylation status have now been identified as a critical component in the initiation of lung cancer, and the detection of DNA methylation is expected to be an important method for the early diagnosis of lung cancer. Nicotine, the principal tobacco alkaloid, directly contributes to lung carcinogenesis through the activation of nicotinic acetylcholine receptors (nAchRs). MATERIALS AND METHODS: To investigate the role of the CHRNB4 gene, which encodes the nAchR β4 subunit that is ubiquitously expressed on lung epithelial cells, we analyzed its methylation status in 266 patients with non-small cell lung cancer (NSCLC) by using methylation-specific polymerase chain reaction and compared it with clinicopathological parameters. RESULTS AND CONCLUSION: The frequency of CHRNB4 unmethylation was 13.5% and 8.3% in malignant and nonmalignant tissues, respectively. CHRNB4 demethylation was associated with upregulation of its mRNA expression and was more frequent in squamous cell carcinoma and pathological stages II-IIIA disease than in adenocarcinoma and pathological stage I disease, respectively (P=0.003 and P=0.01, respectively). Univariate and multivariate analyses showed that CHRNB4 unmethylation was significantly associated with unfavorable overall survival in the entire patient group as well as in men and ever-smokers. These results suggest that epigenetic regulation of CHRNB4 may affect tumor progression and survival in patients with NSCLC. Further investigation into the molecular basis of the role of CHRNB4 in the progression of NSCLC is warranted.
OBJECTIVES:Lung cancer is the leading cause of cancer-related deaths and is currently a major health problem owing to difficulties in diagnosis at the early stage of the disease. Changes in DNA methylation status have now been identified as a critical component in the initiation of lung cancer, and the detection of DNA methylation is expected to be an important method for the early diagnosis of lung cancer. Nicotine, the principal tobacco alkaloid, directly contributes to lung carcinogenesis through the activation of nicotinic acetylcholine receptors (nAchRs). MATERIALS AND METHODS: To investigate the role of the CHRNB4 gene, which encodes the nAchR β4 subunit that is ubiquitously expressed on lung epithelial cells, we analyzed its methylation status in 266 patients with non-small cell lung cancer (NSCLC) by using methylation-specific polymerase chain reaction and compared it with clinicopathological parameters. RESULTS AND CONCLUSION: The frequency of CHRNB4 unmethylation was 13.5% and 8.3% in malignant and nonmalignant tissues, respectively. CHRNB4 demethylation was associated with upregulation of its mRNA expression and was more frequent in squamous cell carcinoma and pathological stages II-IIIA disease than in adenocarcinoma and pathological stage I disease, respectively (P=0.003 and P=0.01, respectively). Univariate and multivariate analyses showed that CHRNB4 unmethylation was significantly associated with unfavorable overall survival in the entire patient group as well as in men and ever-smokers. These results suggest that epigenetic regulation of CHRNB4 may affect tumor progression and survival in patients with NSCLC. Further investigation into the molecular basis of the role of CHRNB4 in the progression of NSCLC is warranted.
Authors: S Lauren Kyte; Wisam Toma; Deniz Bagdas; Julie A Meade; Lesley D Schurman; Aron H Lichtman; Zhi-Jian Chen; Egidio Del Fabbro; Xianjun Fang; John W Bigbee; M Imad Damaj; David A Gewirtz Journal: J Pharmacol Exp Ther Date: 2017-10-17 Impact factor: 4.030
Authors: Marina Chianello Nicolau; Luis Felipe Ribeiro Pinto; Pedro Nicolau-Neto; Paulo Roberto Alves de Pinho; Ana Rossini; Tatiana de Almeida Simão; Sheila Coelho Soares Lima Journal: World J Gastroenterol Date: 2016-08-21 Impact factor: 5.742