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Super‐SILAC based quantitative phosphoproteomics reveals the potential biomarkers in lung cancer
Author(s) -
Hsiao TingFeng,
Wang ChihLiang,
Wu YiCheng,
Wu ChiaChun,
Yu ChiaJung
Publication year - 2019
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.2019.33.1_supplement.lb238
Subject(s) - phosphoproteomics , cancer research , epidermal growth factor receptor , lung cancer , stable isotope labeling by amino acids in cell culture , targeted therapy , adenocarcinoma , medicine , erlotinib , cancer , kinase , biology , proteomics , oncology , protein phosphorylation , protein kinase a , microbiology and biotechnology , biochemistry , gene
Lung adenocarcinoma (ADC) is the most common histological subtype of lung cancer, the leading cause of cancer‐related deaths worldwide. Epidermal growth factor receptor (EGFR) mutations strikingly target lung ADC in East Asia. EGFR tyrosine kinase inhibitor (EGFR‐TKI) has been developed as a targeted therapy for treatment of advanced lung ADC with activating EGFR mutations. Unfortunately, neither druggable targets nor useful biomarkers can be used to benefit ADC patients with wild‐type (WT) EGFR. We herein aimed to identify the differentially expressed phosphoproteins and kinases in ADC tissues with EGFR‐WT. We applied super‐SILAC combined with TiO 2 phosphopeptide enrichment and liquid chromatography‐tandem mass spectrometry to establish the stage‐related phosphoproteome with 20244 phosphopeptides in ADC tissues. The bioinformatics analyses revealed the stage‐dependent phosphorylation profile, upstream signaling and the kinase cascade in ADC tissues. We also observed that the impact of EGF, PTK2B, JAK2, ICAM1, or VEGF on pathogenesis of the early‐ and late‐stage cancers was indeed different. To explore the clinical applications of these dysregulated phosphoproteins in lung ADC, the potential markers were selected for further verifications/validations via western blotting and immunohistochemistry staining. Support or Funding Information Ministry of Science and Technology, Taiwan, R.O.C. (105‐2320‐B‐182‐035‐MY3) and Chang Gung Medical Research Fund (CMRPD1H0081, CMRPD1H0082 and BMRP894). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .