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Profiling stage‐related tissue proteomes to discover potential diagnostic and prognostic biomarkers for lung adenocarcinoma
Author(s) -
Hsu ChiungHung,
Wu ChihChing,
Wang ChihLiang,
Hsueh Chuen,
Wu YiCheng,
Hsu ChiaWei,
Liu ChinChing,
Lai PingChang,
Yu JauSong,
Chang YuSun,
Yu ChiaJung
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb176
Subject(s) - immunohistochemistry , lung cancer , christian ministry , metastasis , adenocarcinoma , medicine , stage (stratigraphy) , biomarker , cancer research , pathology , oncology , cancer , biology , paleontology , philosophy , biochemistry , theology
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 (ERO1Lα, PABPC4, RPS25, TARS, NARS, and RCC1) from 151 proteins with a 1.5‐fold increase in ADC tumors without LN metastasis compared with adjacent normal tissue. These six proteins underwent further verification using immunohistochemical staining and western blotting. The protein levels of these six candidates were overexpressed in tumor tissues compared with the adjacent normal tissue. The area under the receiver operating characteristic curve was 0.864 for the combination of the two potential biomarkers (ERO1Lα and NARS) in discriminating tumor tissues without LN metastasis from adjacent normal tissue. Importantly, ERO1Lα and NARS levels were positively associated with LN metastasis, and ERO1Lα overexpression was correlated with poor patient survival. Moreover, we found that the knockdown of either ERO1Lα or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker dataset for ADC diagnosis/prognosis and reveal novel roles of ERO1Lα and NARS in ADC progression. Support or Funding Information This work was supported by grants from the Ministry of Science and Technology, Taiwan, R.O.C. (101‐2320‐B‐182‐035‐MY3 and 104‐2320‐B‐182‐027), the Chang Gung Medical Research Fund (CMRPD3E0081‐2 and CMRPD1C0092) and the Ministry of Education, Taiwan, R.O.C. (EMRPD1E1401).