In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

摘要: Pleural effusion (PE), a tumor-proximal body fluid, may be promising source for biomarker discovery in human cancers. Because variety of pathological conditions can lead to PE, characterization the relative PE proteomic profiles from different types PEs would accelerate potential biomarkers specifically used diagnose pulmonary disorders. Using quantitative approaches, we identified 772 nonredundant proteins six exudative PEs, including three malignant (MPE, lung, breast, and gastric cancers), one lung cancer paramalignant two benign diseases (tuberculosis pneumonia). Spectral counting was utilized semiquantify protein levels. Principal component analysis, hierarchical clustering, Gene Ontology cellular process analyses revealed differential levels functional profiling each type PE. We 30 candidate with twofold higher (q<0.05) MPEs than PEs. Three markers, MET, DPP4, PTPRF, were further verified by ELISA using 345 samples. The these significantly MPE or area under receiver-operator characteristic curve combined discriminating 0.903. also observed that more clearly discriminated effusions which cytological examination positive they useful rescuing false negative diagnosis nonsmall cell cancer-MPE. Western blotting analysis demonstrated MET overexpression cells contribute elevation soluble MPE. Our results collectively demonstrate utility label-free approaches establishing proteomes provide new database facilitate identification disorder-related biomarkers.