title: Urinary protein biomarkers in the early detection of lung cancer.
abstract: The early detection of lung cancer has the potential to greatly impact disease burden through the timely identification and treatment of affected individuals at a manageable stage of development. The insufficient specificity demonstrated by currently used screening and diagnostic techniques has led to intense investigation into biomarkers as diagnostic tools. Urine may represent a noninvasive alternative matrix for diagnostic biomarker development. We performed an analysis of 242 biomarkers in urines obtained from 83 patients with non-small cell lung carcinomas (NSCLC), 74 patients diagnosed with benign pulmonary conditions, and 77 healthy donors. A large number of significant alterations were observed between the NSCLC and control groups. A multivariate analysis identified a three-biomarker panel consisting of IGFBP-1, sIL-1Ra, CEACAM-1, which discriminated NSCLC from healthy controls with a sensitivity/specificity of 84/95 in an initial training set and 72/100 in an independent validation set. This panel performed well among multiple subtypes of NSCLC and early-stage disease but demonstrated only limited efficacy for the discrimination of NSCLC from benign controls and limited specificity for patients with several other cancers and tuberculosis. These findings demonstrate that urine biomarkers may provide screening and diagnostic properties which exceed those reported for serum biomarkers and approach a level necessary for further clinical development.
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania. Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. lokshina@upmc.edu.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Nolen
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Lomakin
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania.
authors.forename: Adele
authors.initials: A
authors.lastname: Marrangoni
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Velikokhatnaya
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania.
authors.forename: Denise
authors.initials: D
authors.lastname: Prosser
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania. Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Ob/Gyn, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung / Q000652:urine*; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000652:urine*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor