Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

Breast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IPR) is a major player in the regulation of the Ca flux from the endoplasmic reticulum to the cytoplasm. The IPRs (and particularly the IPR3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IPRs as prognostic biomarkers in breast cancer. We found that expression levels of IPR3 and IPR1 (but not IPR2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IPR3 subtype was expressed more strongly than the IPR1 and IPR2 subtypes. Furthermore, the expression of IPR3 (but not of IPR1 or IPR2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IPRs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IPR subtypes, IPR3 expression is upregulated in breast cancer and is correlated with prognostic factors.