Exosomal miRNA profiles for prediction of response to neoadjuvant chemotherapy in breast cancer

• Project/Area Number: 18K16290
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Teikyo University
• Principal Investigator: Matsumoto Akiko 帝京大学, 医学部, 助教 (70573418)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 乳癌 / microRNA / エクソソーム / 術前薬物療法 / 化学療法 / 内分泌療法 / 薬物療法

Outline of Final Research Achievements

We investigated the validity of exosomal miRNAs as biomarkers for the therapeutic effect of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer. Plasma samples were collected before and after NAC and one month after surgery in 98 cases with luminal, triple-negative, and HER2 positive types. Microarray-based expression profiling of miRNAs derived from exosomes in prior-NAC plasma samples of 30 triple-negative patients and plasma samples of 8 healthy controls. In the miRNA microarray analysis, the exosomal miR-142-5p, miR-23a-3p, miR-19a-3p, and miR-130a-3p levels showed marked upregulation in the non-responding group as compared with the responding group and the healthy samples.

Academic Significance and Societal Importance of the Research Achievements

今後更なる化学療法や分子標的薬の開発が進むことが予想される中で、治療効果予測バイオマーカーとしてのmiRNAの意義が示されれば、適切な治療対象群の絞り込みが可能となり、患者の有害事象の軽減、医療経済的な負担軽減につながることが予想される。また、予後予測因子としては、pCRやki67など腫瘍組織における指標が用いられてきたが、血漿中miRNA発現の有用性が示されれば、術前治療開始前により低侵襲に予後予測が可能となる。本研究が個別化治療の実現に寄与し、乳癌の更なる治療成績向上につながることが期待される。

Research Products

• [Presentation] Predicting Axillary Pathologic response to Neoadjuvant Chemotherapy for Node-Positive Breast Cancer: Clinical predictive model by Using MRI and Ultrasound. (2020)
  • Author(s): Akiko Matsumoto
  • Organizer: San Antonio Breast Cancer Symposium
  • Int'l Joint Research
• [Presentation] Omission of Axillary Dissection after Neoadjuvant Chemotherapy for Node-Positive Primary Breast Cancer. (2020)
  • Author(s): Akiko Matsumoto
  • Organizer: European Breast Cancer Conference (EBCC 12)
  • Int'l Joint Research
• [Presentation] Validity of Omission of Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy for Node-Positive Primary Breast Cancer (2019)
  • Author(s): Akiko Matsumoto
  • Organizer: San Antonio Breast Cancer Symposium
  • Int'l Joint Research