Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shiljiazhuang, Hebei 050011, P.R. China.
Breast Center, The Fourth Hospital of Hebei Medical University, Shiljiazhuang, Hebei 050011, P.R. China.
Oncol Rep. 2020 Jun;43(6):2093-2104. doi: 10.3892/or.2020.7564. Epub 2020 Mar 26.
Human epidermal growth factor receptor 2 (HER2) is composed of an extracellular domain (ECD), a lipophilic transmembrane region and an intracellular domain (ICD). The most commonly used method to determine the status of HER2 is immunohistochemistry. However, false‑negative results are sometimes given, which causes some patients to lose the opportunity for anti‑HER2 therapy. We found that calpain‑10 may prohibit HER2‑ECD into peripheral blood resulting in a HER2‑negative result by the immunohistochemical method. We enrolled 289 patients into our experiment to assess the relationship between sHER2‑ECD and calpain‑10. The results showed that there was a positive correlation between sHER2‑ECD and calpain‑10. Moreover, we also investigated the prognostic values of sHER2‑ECD and calpain‑10 in breast cancer patients. According to the follow‑up results, positive sHER2‑ECD and tissue calpain‑10 were indicative of a poor prognosis in breast cancer patients. Subsequently, we further validated the relationship between the two molecules in in vitro experiments. In the in vitro experiments, the level of HER2‑ECD in the culture medium was increased or decreased with a decrease or increase in calpain‑10 by transfection technology, showing an inverse association. The results indicated that sHER2‑ECD and tissue calpain‑10 levels were powerful factors to assess the status of HER2. In combination with tissue HER2 detection, the occurrence of false‑negative HER2 was reduced, providing patients with additional treatment opportunities. In conclusion, sHER2‑ECD and tissue calpain‑10 may be used as new prognostic indices for breast cancer.
人表皮生长因子受体 2（HER2）由细胞外结构域（ECD）、疏水性跨膜区和细胞内结构域（ICD）组成。最常用于确定 HER2 状态的方法是免疫组织化学。然而，有时会给出假阴性结果，导致一些患者失去接受抗 HER2 治疗的机会。我们发现钙蛋白酶 10 可能通过阻止 HER2-ECD 进入外周血而导致免疫组织化学方法 HER2 阴性结果。我们招募了 289 名患者进行实验，以评估 sHER2-ECD 与钙蛋白酶 10 之间的关系。结果表明，sHER2-ECD 与钙蛋白酶 10 之间存在正相关。此外，我们还研究了 sHER2-ECD 和钙蛋白酶 10 在乳腺癌患者中的预后价值。根据随访结果，sHER2-ECD 和组织钙蛋白酶 10 阳性提示乳腺癌患者预后不良。随后，我们在体外实验中进一步验证了这两个分子之间的关系。在体外实验中，通过转染技术降低或增加钙蛋白酶 10 的水平，培养基中 HER2-ECD 的水平随之增加或降低，呈负相关。结果表明，sHER2-ECD 和组织钙蛋白酶 10 水平是评估 HER2 状态的有力因素。与组织 HER2 检测相结合，减少了 HER2 假阴性的发生，为患者提供了额外的治疗机会。总之，sHER2-ECD 和组织钙蛋白酶 10 可作为乳腺癌新的预后指标。
