title: Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis.
abstract: The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
authors.forename: Lijia
authors.initials: L
authors.lastname: Ma
authors.forename: Chunni
authors.initials: C
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Zhiji
authors.initials: Z
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Sijia
authors.initials: S
authors.lastname: Wu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhuang
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.forename: Chazhen
authors.initials: C
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs