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

Arthur Foulon (1, 2) , Pierre Rybarczyk (1, 2) , Nicolas Jonckheere (3, 4) , Eva Brabencova (5, 6) , Henri Sevestre (1, 2) , Halima Ouadid-Ahidouch (2) , Lise Rodat-Despoix (2)

1 CHU Amiens-Picardie
2 LPCM - Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667
3 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 Institut Jean Godinot [Reims]
6 UNICANCER

The inositol-trisphosphate receptor (IP3R) is a key player in physiological and pathological intracellular calcium signaling. The objective of the present study was to assess the putative value of the three IP3R subtypes as prognostic biomarkers in breast cancer. We found that IP(3)R3 is the most strongly expressed subtype in breast cancer tissue. Furthermore, IP(3)R3 and IP(3)R1 are significantly more expressed in invasive breast cancer tissue than in non-tumor tissue. In contrast to IP(3)R1 and IP(3)R2, the expression of IP(3)R3 was positively correlated with prognostic factors including tumor size, regional node invasion, histologic grade, proliferation index, and hormonal status. By analyzing public databases, we found that the expression of all IP3R subtypes is significantly correlated with the overall survival and disease-free survival of patients with breast cancer. We conclude that relative to the other two IP3R subtypes, IP(3)R3 expression is upregulated in breast cancer and is correlated with prognostic factors. We strongly believe that our results will open up new perspectives with regard to the link between IP(3)Rs and breast cancer aggressiveness. 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 Ca2+ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP3R) is a major player in the regulation of the Ca2+ flux from the endoplasmic reticulum to the cytoplasm. The IP(3)Rs (and particularly the IP(3)R3 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 IP(3)Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP(3)R3 and IP(3)R1 (but not IP(3)R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP(3)R3 subtype was expressed more strongly than the IP(3)R1 and IP(3)R2 subtypes. Furthermore, the expression of IP(3)R3 (but not of IP(3)R1 or IP(3)R2) 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 IP(3)Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP3R subtypes, IP(3)R3 expression is upregulated in breast cancer and is correlated with prognostic factors.

Mots clés: inositol 1; 4-5 trisphosphate; breast cancer; invasive prognostic marker; inositol 1

Domaines: Cancer; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Arthur Foulon, Pierre Rybarczyk, Nicolas Jonckheere, Eva Brabencova, Henri Sevestre, et al.. Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?. International Journal of Molecular Sciences, 2022, 23 (6), pp.2962. ⟨10.3390/ijms23062962⟩. ⟨hal-04326232⟩