title: Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).
abstract: Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients.
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Zhenrong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Qing
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: deruoliu@vip.sina.com.
authors.forename: Deruo
authors.initials: D
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta
keywords: APC; Methylation; Non-small cell lung cancer; Prognosis; RAR-β