title: Integrating DNA methylation and microRNA biomarkers in sputum for lung cancer detection.
abstract: Abnormal microRNA (miRNA) expressions and promoter methylation of genes detected in sputum may provide biomarkers for non-small lung cancer (NSCLC). Here, we evaluate the individual and combined analysis of the two classes of sputum molecular biomarkers for NSCLC detection.
  
  
  
  We analyze expression of 3 miRNAs (miR-21, miR-31, and miR-210) and methylation of 3 genes (RASSF1A,PRDM14, and3OST2), which were previously identified as potential biomarkers for NSCLC, in sputum of a set of 117 stage I NSCLC patients and 174 cancer-free smokers. The results are validated in a different set of 144 stage I NSCLC patients and 171 controls. The panel of 3 miRNA biomarkers has 81.5 % sensitivity and 85.9 % specificity; the panel of 3 methylation biomarkers displays 82.9 % sensitivity and 76.4 % specificity for NSCLC detection. Integrated analysis of 2 miRNAs (miR-31 and miR-210) and 2 genes (RASSF1Aand3OST2) yields higher sensitivity (87.3 %) and specificity (90.3 %) compared with the individual panels of the biomarkers (P< 0.05). Combined analysis of all the 3 miRNAs and 3 genes does not have performance superior to that of the panel of 2 miRNAs and 2 genes (P> 0.05). The performance of combined use of the two classes of biomarkers was confirmed in the validation set.
  
  
  
  The integration of two different classes of biomarkers synergistically improves both the sensitivity and the specificity for the early detection of NSCLC.
authors: Department of Surgery, Jiangsu Province Hospital of Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023 China.
authors: Yun
authors: Y
authors: Su
authors: Department of Epidemiology, University of Maryland School of Medicine, Baltimore, MD USA.
authors: HongBin
authors: H
authors: Fang
authors: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD USA.
authors: Feng
authors: F
authors: Jiang
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D013183:Sputum / Q000737:chemistry*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; C524724:PRDM14 protein, human; C411762:RASSF1 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: DNA methylation; Diagnosis; Lung cancer; MicroRNA; Sputum