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Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules from Lung Adenocarcinoma.
Codreanu, Simona G; Hoeksema, Megan D; Slebos, Robbert J C; Zimmerman, Lisa J; Rahman, S M Jamshedur; Li, Ming; Chen, Sheau-Chiann; Chen, Heidi; Eisenberg, Rosana; Liebler, Daniel C; Massion, Pierre P.
Afiliación
  • Codreanu SG; Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Slebos RJC; Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Zimmerman LJ; Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Li M; Department of Biostatistics, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Chen SC; Center for Quantitative Sciences, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Chen H; Department of Biostatistics, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Eisenberg R; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Liebler DC; Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
  • Massion PP; Department of Cancer Biology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
J Proteome Res ; 16(9): 3266-3276, 2017 09 01.
Article en En | MEDLINE | ID: mdl-28731711
We hypothesized that distinct protein expression features of benign and malignant pulmonary nodules may reveal novel candidate biomarkers for the early detection of lung cancer. We performed proteome profiling by liquid chromatography-tandem mass spectrometry to characterize 34 resected benign lung nodules, 24 untreated lung adenocarcinomas (ADCs), and biopsies of bronchial epithelium. Group comparisons identified 65 proteins that differentiate nodules from ADCs and normal bronchial epithelium and 66 proteins that differentiate ADCs from nodules and normal bronchial epithelium. We developed a multiplexed parallel reaction monitoring (PRM) assay to quantify a subset of 43 of these candidate biomarkers in an independent cohort of 20 benign nodules, 21 ADCs, and 20 normal bronchial biopsies. PRM analyses confirmed significant nodule-specific abundance of 10 proteins including ALOX5, ALOX5AP, CCL19, CILP1, COL5A2, ITGB2, ITGAX, PTPRE, S100A12, and SLC2A3 and significant ADC-specific abundance of CEACAM6, CRABP2, LAD1, PLOD2, and TMEM110-MUSTN1. Immunohistochemistry analyses for seven selected proteins performed on an independent set of tissue microarrays confirmed nodule-specific expression of ALOX5, ALOX5AP, ITGAX, and SLC2A3 and cancer-specific expression of CEACAM6. These studies illustrate the value of global and targeted proteomics in a systematic process to identify and qualify candidate biomarkers for noninvasive molecular diagnosis of lung cancer.
Asunto(s)
Adenocarcinoma/diagnóstico; Biomarcadores de Tumor/genética; Regulación Neoplásica de la Expresión Génica; Neoplasias Pulmonares/diagnóstico; Proteínas de Neoplasias/genética; Nódulo Pulmonar Solitario/diagnóstico; Proteínas Activadoras de la 5-Lipooxigenasa/genética; Proteínas Activadoras de la 5-Lipooxigenasa/metabolismo; Adenocarcinoma/genética; Adenocarcinoma/metabolismo; Adenocarcinoma/patología; Adenocarcinoma del Pulmón; Adulto; Anciano; Antígenos CD/genética; Antígenos CD/metabolismo; Araquidonato 5-Lipooxigenasa/genética; Araquidonato 5-Lipooxigenasa/metabolismo; Biomarcadores de Tumor/metabolismo; Antígenos CD11/genética; Antígenos CD11/metabolismo; Moléculas de Adhesión Celular/genética; Moléculas de Adhesión Celular/metabolismo; Diagnóstico Diferencial; Femenino; Proteínas Ligadas a GPI/genética; Proteínas Ligadas a GPI/metabolismo; Transportador de Glucosa de Tipo 3/genética; Transportador de Glucosa de Tipo 3/metabolismo; Humanos; Cadenas alfa de Integrinas/genética; Cadenas alfa de Integrinas/metabolismo; Neoplasias Pulmonares/genética; Neoplasias Pulmonares/metabolismo; Neoplasias Pulmonares/patología; Masculino; Persona de Mediana Edad; Proteínas de Neoplasias/metabolismo; Proteómica/métodos; Mucosa Respiratoria/metabolismo; Mucosa Respiratoria/patología; Nódulo Pulmonar Solitario/genética; Nódulo Pulmonar Solitario/metabolismo; Nódulo Pulmonar Solitario/patología; Espectrometría de Masas en Tándem; Análisis de Matrices Tisulares; Transcriptoma
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenocarcinoma / Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Nódulo Pulmonar Solitario / Neoplasias Pulmonares / Proteínas de Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenocarcinoma / Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / Nódulo Pulmonar Solitario / Neoplasias Pulmonares / Proteínas de Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos