title: Sputum microRNA biomarkers for identifying lung cancer in indeterminate solitary pulmonary nodules.
abstract: OBJECTIVE
  The early detection of lung cancer in heavy smokers by low-dose CT (LDCT) can reduce the mortality. However, LDCT screening increases the number of indeterminate solitary pulmonary nodules (SPN) in asymptomatic individuals, leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could provide potential biomarkers for lung cancer. Here, we aimed to develop sputum miRNA biomarkers for diagnosis of malignant SPNs.
  
  
  METHODS
  Using quantitative RT-PCR, we evaluated expressions of 13 sputum miRNAs, previously identified sputum miRNA signatures of lung cancer, in a training set of 122 patients with either malignant (n = 60) or benign SPNs (n = 62) to define a panel of biomarkers. We then validated the biomarker panel in an internal testing set of 136 patients with either malignant (n = 67) or benign SPNs (n = 69), and an external testing cohort of 155 patients with either malignant (n = 76) or benign SPNs (n = 79).
  
  
  RESULTS
  In the training set, a panel of three miRNA biomarkers (miRs21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84% specificity for identifying malignant SPNs. The sensitivity and specificity of the biomarkers in the two independent testing cohorts were 82.09% and 88.41%, 80.52% and 86.08%, respectively, confirming the diagnostic value.
  
  
  CONCLUSIONS
  Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China. xinglingxiao@hotmail.com fjiang@som.umaryland.edu.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Guarnera
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Howard
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Ling
authors.initials: L
authors.lastname: Cai
authors.affiliation: Nevada Cancer Center, Las Vegas, Nevada.
authors.forename: Rixin
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Sanford A
authors.initials: SA
authors.lastname: Stass
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland. xinglingxiao@hotmail.com fjiang@som.umaryland.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012372:ROC Curve; D003074:Solitary Pulmonary Nodule / Q000175:diagnosis* / Q000378:metabolism; D013183:Sputum / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs