Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.
Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging.
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DOI：
10.1038/srep14322
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发表时间：
2015-09-22
影响因子：
4.6
通讯作者：
Ohuchi N
中科院分区：
文献类型：
--
作者：
Gonda K;Miyashita M;Higuchi H;Tada H;Watanabe TM;Watanabe M;Ishida T;Ohuchi N
在乳腺癌中，通过抗HER 2抗体药物曲妥珠单抗和帕妥珠单抗的临床应用，人表皮生长因子受体2（HER 2）阳性患者（20-25%）的预后得到了显著改善。然而，具有不良预后的HER 2阴性病例的临床结果没有改善，并且迫切需要新的治疗性抗体药物或预后的诊断分子标志物。在这里，我们靶向蛋白酶激活受体1（PAR 1）作为HER 2阴性患者的新生物标志物。所开发的抗PAR 1抗体通过基质金属蛋白酶1抑制PAR 1活化，从而防止癌细胞迁移和侵袭。为了使用抗体估计HER 2阴性患者组织中的PAR 1表达水平，开发了使用荧光纳米颗粒或量子点（QD）的用户友好的免疫组织化学。以前，免疫组织化学与量子点的影响，组织自发荧光，定量测量非常困难。我们通过使用自体荧光减影图像和单QD成像显着提高了免疫组化与QD的定量灵敏度。免疫组化结果显示，PAR 1表达与HER 2阴性乳腺癌患者的无复发生存期密切相关。因此，开发的抗PAR 1抗体是用作抗癌药物和HER 2阴性患者的预后生物标志物的强有力的候选者。
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.