title: A panel of promoter methylation markers for invasive and noninvasive early detection of NSCLC using a quantum dots-based FRET approach.
abstract: Non-small-cell lung cancer (NSCLC) leads to a significant proportion of cancer-related deaths, and early detection of NSCLC can significantly increase cancer survival rates. A promising approach has been studied to exploit DNA methylation, which is closely correlated to early cancer diagnosis. Herein, in order to realize the early detection of NSCLC, we utilized the developed quantum dots-based (QDs-based) fluorescence resonance energy transfer (FRET) nanosensor technique to analyze the promoter methylation in early stage NSCLC tissue samples and noninvasive bronchial brushing specimens. Using this method, the methylation levels can be quantitatively determined by measuring the signal amplification during FRET. A panel of three tumor suppressor genes (PCDHGB6, HOXA9 and RASSF1A) was assessed in 50 paired early stage NSCLC and their adjacent nontumorous tissue (NT) samples, and 50 early stage NSCLC bronchial brushing and normal specimens. The combined detection was able to identify not only tissue samples but noninvasive bronchial brushing specimens from control cases with a high degree of sensitivity of 92% (AUC=0.977, P<0.001) and 80% (AUC=0.907, P<0.001) respectively, indicating the versatility of promoter expression in invasive and noninvasive NSCLC samples. Therefore this approach can be used to sensitively analyze the methylation levels of cancer-related genes, which might be a potential tool for noninvasive early clinical diagnosis of cancers.
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China; Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Departments of Anesthesiology and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hailei
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Fangming
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Medicine/Cancer Prevention, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China. Electronic address: zhongxh@ecust.edu.cn.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200050, China. Electronic address: hjmao@mail.sim.ac.cn.
authors.forename: Hongju
authors.initials: H
authors.lastname: Mao
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D055088:Early Detection of Cancer; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D045663:Quantum Dots / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor
keywords: Bronchial brushing; Early detection; FRET; NSCLC; Promoter methylation; Quantum dots