Premium
Discovering drug resistance‐associated biomarkers from malignant pleural effusion of lung cancer by quantitative proteomic approaches
Author(s) -
Yu ChiaJung,
Chiou IenChiuam,
Wang ChihLiang,
Hsiao TingFeng
Publication year - 2018
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.2018.32.1_supplement.lb107
Subject(s) - medicine , lung cancer , epidermal growth factor receptor , drug resistance , pleural effusion , oncology , erlotinib , chemotherapy , drug , malignant pleural effusion , cancer , pharmacology , biology , microbiology and biotechnology
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have been approved for the treatment of patients with advanced lung adenocarcinoma (ADC) harboring EGFR activating mutations. Although the EGFR‐TKIs or combined treatments of EGFR‐TKIs and chemotherapy would benefit patients, the following drug‐resistant issue eventually led to the poor survival of cancer patients. Therefore, it is important to search the drug resistance‐associated biomarkers for monitoring the treatment efficacy and/or prognosis in lung ADC. We herein applied high‐abundant protein removal system and iTRAQ‐based quantitative proteomics approach to generate the drug resistance‐associated malignant pleural effusion (MPE) proteome data sets from lung ADC patients who were sensitive, resistant to TKI, or resistant to TKI/chemotherapy. Among the 565 quantified MPE proteins, five potential biomarkers (CEACAM5, DMBT1, HGFAC, MMP3, CDHP) were isolated for preclinical validation using ELISA. The MPE levels of these five candidates were increased in patients with drug‐resistant as compared to patients with treatment naïve. Importantly, the levels of MMP3 and CDHP in serum samples were significantly associated with patients' survival and treatment efficacy. Our results collectively provide the potential biomarkers for prediction of drug resistance as well as prognosis in lung ADC. Support or Funding Information This work was financially supported by grants from the Ministry of Science and Technology, Taiwan (104‐2320‐B‐182‐027 and 105‐2320‐B‐182‐035‐MY3), and from Chang Gung Memorial Hospital, Taoyuan, Taiwan (BMRP894). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .