國家衛生研究院 NHRI:Item 3990099045/12594
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    题名: Integrative omics analysis reveals soluble cadherin-3 as a survival predictor and an early monitoring marker of EGFR tyrosine kinase inhibitor therapy in lung cancer
    作者: Hsiao, TF;Wang, CL;Wu, YC;Feng, HP;Chiu, YC;Lin, HY;Liu, KJ;Chang, GC;Chien, KY;Yu, JS;Yu, CJ
    贡献者: National Institute of Cancer Research
    摘要: INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit advanced lung adenocarcinoma (ADC) patients harboring activating EGFR mutations. We aimed to identify biomarkers to monitor and predict the progression of patients receiving EGFR-TKIs via a comprehensive omic analysis. METHODS: We applied quantitative proteomics to generate the TKI resistance-associated pleural effusion (PE) proteome from ADC patients with or without EGFR-TKI resistance. Candidates were selected from integrated genomic and proteomic datasets. The PE (n=33) and serum (n=329) levels of potential biomarkers were validated with enzyme-linked immunosorbent assays (ELISAs). Western blotting was applied to detect protein expression in tissues, PEs and a cell line. Gene knockdown, TKI treatment and proliferation assays were used to determine EGFR-TKI sensitivity. Progression-free survival (PFS) and overall survival (OS) were assessed to evaluate the prognostic values of the potential biomarkers. RESULTS: Fifteen proteins were identified as potential biomarkers of EGFR-TKI resistance. Cadherin-3 (CDH3) was overexpressed in ADC tissues compared to normal tissues. CDH3 knockdown enhanced EGFR-TKI sensitivity in ADC cells. The PE level of soluble CDH3 (sCDH3) was increased in patients with resistance. The altered sCDH3 serum level reflected the efficacy of EGFR-TKI after one month of treatment (n=43). Baseline sCDH3 was significantly associated with PFS and OS in ADC patients after EGFR-TKI therapy (n=76). Moreover, sCDH3 was positively associated with tumor stage in non-small cell lung cancer (NSCLC) (n=272). CONCLUSIONS: We provide useful marker candidates for drug resistance studies. sCDH3 is a survival predictor and real-time indicator of treatment efficacy in ADC patients treated with EGFR-TKIs.
    日期: 2020-07
    關聯: Clinical Cancer Research. 2020 Jul;26(13):3220-3229.
    Link to: http://dx.doi.org/10.1158/1078-0432.Ccr-19-3972
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1078-0432&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000546016400018
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85087469927
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