Deep learning-assisted monitoring of trastuzumab efficacy in HER2-Overexpressing breast cancer via SERS immunoassays of tumor-derived urinary exosomal biomarkers.

Journal: Biosensors & bioelectronics
PMID:

Abstract

Monitoring drug efficacy is significant in the current concept of companion diagnostics in metastatic breast cancer. Trastuzumab, a drug targeting human epidermal growth factor receptor 2 (HER2), is an effective treatment for metastatic breast cancer. However, some patients develop resistance to this therapy; therefore, monitoring its efficacy is essential. Here, we describe a deep learning-assisted monitoring of trastuzumab efficacy based on a surface-enhanced Raman spectroscopy (SERS) immunoassay against HER2-overexpressing mouse urinary exosomes. Individual Raman reporters bearing the desired SERS tag and exosome capture substrate were prepared for the SERS immunoassay; SERS tag signals were collected to prepare deep learning training data. Using this deep learning algorithm, various complicated mixtures of SERS tags were successfully quantified and classified. Exosomal antigen levels of five types of cell-derived exosomes were determined using SERS-deep learning analysis and compared with those obtained via quantitative reverse transcription polymerase chain reaction and western blot analysis. Finally, drug efficacy was monitored via SERS-deep learning analysis using urinary exosomes from trastuzumab-treated mice. Use of this monitoring system should allow proactive responses to any treatment-resistant issues.

Authors

  • Jinyoung Kim
    R&D Center, VUNO, Seoul, Republic of Korea.
  • Hye Young Son
    Department of Radiology, Yonsei University, Seoul, 03772, Republic of Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, 03772, Republic of Korea; YUHS-KRIBB Medical Convergence Research Institute, Yonsei University, Seoul, 03772, Republic of Korea; Department of Biochemistry & Molecular Biology, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea.
  • Sojeong Lee
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Hyun Wook Rho
    Department of Radiology, Yonsei University, Seoul, 03772, Republic of Korea.
  • Ryunhyung Kim
    Department of Neurology, New York University School of Medicine.
  • Hyein Jeong
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Chaewon Park
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Byeonggeol Mun
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Yesol Moon
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Eunji Jeong
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea.
  • Eun-Kyung Lim
    Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
  • Seungjoo Haam
    Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seoul, 120-749, Republic of Korea. Electronic address: haam@yonsei.ac.kr.