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A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

Author

Listed:
  • Hui Deng

    (Sichuan University
    Sichuan University
    Sichuan University)

  • Qian Lei

    (Sichuan University
    Sichuan University
    Sichuan University)

  • Chengdi Wang

    (Sichuan University)

  • Zhoufeng Wang

    (Sichuan University
    Sichuan University)

  • Hai Chen

    (Sichuan University
    Sichuan University)

  • Gang Wang

    (Sichuan University)

  • Na Yang

    (Sichuan University)

  • Dan Huang

    (Sichuan University)

  • Quanwei Yu

    (Sichuan University)

  • Mengling Yao

    (Sichuan University)

  • Xue Xiao

    (Sichuan University)

  • Guonian Zhu

    (Sichuan University)

  • Cheng Cheng

    (Sichuan University)

  • Yangqian Li

    (Sichuan University)

  • Feng Li

    (Sichuan University)

  • Panwen Tian

    (Sichuan University)

  • Weimin Li

    (Sichuan University
    Sichuan University
    Sichuan University)

Abstract

Therapeutic responses of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) are known to be associated with EGFR mutations. However, a proportion of NSCLCs carrying EGFR mutations still progress on EGFR-TKI underlining the imperfect correlation. Structure-function-based approaches have recently been reported to perform better in retrospectively predicting patient outcomes following EGFR-TKI treatment than exon-based method. Here, we develop a multicolor fluorescence-activated cell sorting (FACS) with an EGFR-TKI-based fluorogenic probe (HX103) to profile active-EGFR in tumors. HX103-based FACS shows an overall agreement with gene mutations of 82.6%, sensitivity of 81.8% and specificity of 83.3% for discriminating EGFR-activating mutations from wild-type in surgical specimens from NSCLC patients. We then translate HX103 to the clinical studies for prediction of EGFR-TKI sensitivity. When integrating computed tomography imaging with HX103-based FACS, we find a high correlation between EGFR-TKI therapy response and probe labeling. These studies demonstrate HX103-based FACS provides a high predictive performance for response to EGFR-TKI, suggesting the potential utility of an EGFR-TKI-based probe in precision medicine trials to stratify NSCLC patients for EGFR-TKI treatment.

Suggested Citation

  • Hui Deng & Qian Lei & Chengdi Wang & Zhoufeng Wang & Hai Chen & Gang Wang & Na Yang & Dan Huang & Quanwei Yu & Mengling Yao & Xue Xiao & Guonian Zhu & Cheng Cheng & Yangqian Li & Feng Li & Panwen Tian, 2022. "A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34627-5
    DOI: 10.1038/s41467-022-34627-5
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