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  • [Clin Cancer Res.] RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy for Resected Non-small Cell Lung Cancer.

    The University of Texas MD Anderson Cancer Center / Steven H. Lin*

  • 출처
    Clin Cancer Res.
  • 등재일
    2018 Jan 15
  • 저널이슈번호
    24(2):341-350.
  • 내용

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    Abstract

    Purpose: 

    Although postoperative radiotherapy is often used to maintain local control after surgical resection and chemotherapy for locally advanced non-small cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain problematic. The mechanisms of therapeutic resistance remain poorly understood.

    Experimental Design: 

    We used reverse-phase protein arrays (RPPA) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines to categorize pathways that may contribute to radiation resistance. Significant markers identified by RPPA were further analyzed in tissue microarrays (TMA) of specimens from 127 patients with NSCLC who had received surgery before receiving postoperative radiotherapy. Cox regression analysis and log-rank tests were used to identify potential predictive factors. We then validated the biological function of the markers in NSCLC cell lines in vitro

    Results:

    Of the 170 proteins or phospho-proteins profiled, a subset of 12 proteins was found to correlate with radiation response parameters. TMA analysis of the 12 proteins showing the greatest differences in expression in the RPPA analysis demonstrated that RAD50 had the strongest correlation with distant relapse-free survival, locoregional relapse-free survival, and disease-free survival in patients with NSCLC. We confirmed that knockdown of RAD50 sensitized NSCLC cells to radiation and that upregulation of RAD50 increased radioresistance in in vitroexperiments.

    Conclusions: 

    Upregulated RAD50 may be a predictor of radioresistance in patients with lung cancer who received radiotherapy. 

     

     

    Author information

    Wang Y1,2, Gudikote J3, Giri U3, Yan J4, Deng W5, Ye R2, Jiang W5, Li N1, Hobbs BP6, Wang J7, Swisher SG8, Fujimoto J9, Wistuba II9, Komaki R5, Heymach JV3, Lin SH10,5.

    1 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    2 The University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, Texas.
    3 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    4 Oncology Research for Biologics and Immunotherapy Translation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    5 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    6 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    7 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    8 Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    9 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
    10 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. SHLin@mdanderson.org.

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