Centre de Gynécologie-Obstétrique, Université Picardie Jules Verne, CHU Amiens Picardie, F-80089 Amiens, France.
Laboratoire de Physiologie Cellulaire et Moléculaire, UR-UPJV-4667, Université Picardie Jules Verne, F-80090 Amiens, France.
Int J Mol Sci. 2022 Mar 9;23(6):2962. doi: 10.3390/ijms23062962.
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.
乳腺癌是全球和法国女性癌症死亡的主要原因。疾病的预后和治疗因乳腺癌亚型的不同而不同，疾病的结局取决于许多预后因素。离子通量（尤其是 Ca 通量）的失调涉及许多病理生理过程，包括癌变。在细胞内，肌醇三磷酸受体（IPR）是调节内质网到细胞质中 Ca 通量的主要参与者。已知 IPR（特别是 IPR3 亚型）参与乳腺癌细胞系的增殖、迁移和侵袭过程。本研究的目的是评估 IPR 作为乳腺癌预后生物标志物的潜在价值。我们发现，与同一患者的非肿瘤组织相比，无特殊类型浸润性乳腺癌中 IPR3 和 IPR1（但不是 IPR2）的表达水平明显更高。然而，IPR3 亚型的表达强度强于 IPR1 和 IPR2 亚型。此外，IPR3（但不是 IPR1 或 IPR2）的表达与肿瘤大小、区域淋巴结浸润、组织学分级、增殖指数和激素受体状态等预后因素呈正相关。在对公共数据库的分析中，我们发现所有 IPR 类型与乳腺癌患者的总生存和无进展生存均显著相关。我们得出结论，与其他两种 IPR 亚型相比，IPR3 在乳腺癌中的表达上调，并与预后因素相关。
