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Sci Rep. 2015 Sep 22;5:14322. doi: 10.1038/srep14322.

Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.

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Department of Medical Physics, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Department of Surgical Oncology, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Department of Physics, Graduate School of Science, University of Tokyo, Hongo Bunkyou-ku Tokyo 113-0033, Japan.
Laboratory for Comprehensive Bioimaging, RIKEN Quantitative Biology Center, 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan.
Department of Pathology, Tohoku University Hospital, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.


In breast cancer, the prognosis of human epidermal growth factor receptor 2 (HER2)-positive patients (20-25%) has been dramatically improved by the clinical application of the anti-HER2 antibody drugs trastuzumab and pertuzumab. However, the clinical outcomes of HER2-negative cases with a poor prognosis have not improved, and novel therapeutic antibody drugs or diagnostic molecular markers of prognosis are urgently needed. Here, we targeted protease-activated receptor 1 (PAR1) as a new biomarker for HER2-negative patients. The developed anti-PAR1 antibody inhibited PAR1 activation by matrix metalloprotease 1 and thereby prevented cancer-cell migration and invasion. To estimate PAR1 expression levels in HER2-negative patient tissues using the antibody, user-friendly immunohistochemistry with fluorescence nanoparticles or quantum dots (QDs) was developed. Previously, immunohistochemistry with QDs was affected by tissue autofluorescence, making quantitative measurement extremely difficult. We significantly improved the quantitative sensitivity of immunohistochemistry with QDs by using an autofluorescence-subtracted image and single-QD imaging. The immunohistochemistry showed that PAR1 expression was strongly correlated with relapse-free survival time in HER2-negative breast cancer patients. Therefore, the developed anti-PAR1 antibody is a strong candidate for use as an anticancer drug and a prognostic biomarker for HER2-negative patients.

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