Clinical significance of sHER2-ECD and calpain-10 expression in tumor tissues of patients with breast cancer

Abstract

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.