title: Comprehensive proteome analysis of malignant pleural effusion for lung cancer biomarker discovery by using multidimensional protein identification technology.
abstract: Malignant pleural effusion (MPE) obtained from lung adenocarcinoma may contain potentially useful biomarkers for detection of lung cancer. In this study, we used a removal system for high-abundance proteins followed by one-dimensional SDS-PAGE combined with nano-LC-MS/MS to generate a comprehensive MPE proteome data set with 482 nonredundant proteins. Next, we integrated the MPE proteome and secretome data sets from three adenocarcinoma cell lines, with a view to identifying potential PE biomarkers originating from malignant cells. Four potential candidates, alpha-2-HS-glycoprotein (AHSG), angiogenin, cystatin-C, and insulin-like growth factor-binding protein 2, (IGFBP2), were isolated for preclinical validation using ELISA. Both AHSG and IGFBP2 levels were increased in lung patients with MPE (n = 68), compared to those with nonmalignant pleural effusion (n = 119). Notably, the IGFBP2 level was higher in MPE, compared with that in benign diseases (bacteria pneumonia and tuberculosis pleuritis), and significantly associated with malignancy, regardless of the cancer type. Our data additionally support an extracellular function of IGFBP2 in migration in lung cancer cells. These findings collectively suggest that the adenocarcinoma MPE proteome provides a useful data set for malignancy biomarker research.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University , Tao-Yuan, Taiwan. yucj1124@mail.cgu.edu.tw
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Wang
authors.forename: Chi-De
authors.initials: CD
authors.lastname: Chen
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Dan
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Wu
authors.forename: I-Neng
authors.initials: IN
authors.lastname: Lee
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D016208:Databases, Factual; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018971:Insulin-Like Growth Factor Binding Protein 2; D060749:alpha-2-HS-Glycoprotein