title: Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma.
abstract: Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression.
authors.affiliation: From the ‡Graduate Institute of Biomedical Sciences.
authors.forename: Chiung-Hung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan;
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan; **Department of Pathology.
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.affiliation: ⦀School of Medicine, College of Medicine, ‡‡Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.affiliation: §§Department of Thoracic Surgery, and.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Wu
authors.affiliation: §Department of Medical Biotechnology and Laboratory Science, and ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan; §§§Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Wu
authors.affiliation: From the ‡Graduate Institute of Biomedical Sciences.
authors.forename: Chin-Ching
authors.initials: CC
authors.lastname: Liu
authors.affiliation: From the ‡Graduate Institute of Biomedical Sciences, ¶Department of Cell and Molecular Biology, Chang Gung University, Tao-Yuan, Taiwan; ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan;
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.affiliation: From the ‡Graduate Institute of Biomedical Sciences, ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan;
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: From the ‡Graduate Institute of Biomedical Sciences, ¶Department of Cell and Molecular Biology, Chang Gung University, Tao-Yuan, Taiwan; ‖Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan; ‡‡Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, yucj1124@mail.cgu.edu.tw.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D001226:Aspartate-tRNA Ligase / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D010088:Oxidoreductases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D012346:RNA, Transfer, Amino Acyl; C405327:ERO1A protein, human; D010088:Oxidoreductases; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase