Systematic analysis of the expression and prognostic value of ITPR1 and correlation with tumor infiltrating immune cells in breast cancer

Abstract

Background ITPR1 is a key gene for autophagy, but its biological function is still unclear, and there are few studies on the correlation between ITPR1 gene expression and the occurrence and development of breast cancer. Methods Analyze the expression of ITPR1 through online databases such as Oncomine and TIMER. Kaplan–Meier plotter and other databases were used to evaluate the impact of ITPR1 on clinical prognosis. The expression of ITPR1 in analysis of 145 cases of breast cancer and 30 cases of adjacent normal tissue was detected by Immunohistochemistry. Statistical analysis was used to evaluate the clinical relevance and prognostic significance of abnormally expressed proteins. And the Western Blot was used to detect the expression of ITPR1 between breast cancer tissues and cells. The TIMER database studied the relationship between ITPR1 and cancer immune infiltration. And used the ROC plotter database to predict the response of ITPR1 to chemotherapy, endocrine therapy and anti-HER2 therapy in patients with breast cancer. Results Compared with normal breast samples, ITPR1 was significantly lower in patients with breast cancer. And the increased expression of ITPR1 mRNA was closely related to longer overall survival (OS), distant metastasis free survival (DMFS), disease specific survival (DSS) and relapse free survival (RFS) in breast cancer. And the expression level of ITPR1 was higher in patients treated with chemotherapy than untreated patients. In addition, the expression of ITPR1 was positively correlated with related gene markers of immune cells in different types of breast cancer, especially with BRCA basal tissue breast cancer. Conclusion ITPR1 was lower expressed in breast cancer. The higher expression of ITPR1 suggested favorable prognosis for patients. ITPR1 was related to the level of immune infiltration, especially in BRCA-Basal patients. All research results indicated that ITPR1 might affect breast cancer prognosis and participate in immune regulation. In short, ITPR1 might be a potential target for breast cancer therapy.

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

“…ITPR1 is an endoplasmic reticulum (ER) Ca 2+ channel which is activated by inositol 1,4,5-trisphosphate (IP3) second messenger and modulates intracellular calcium homeostasis and signaling in the cell 25 . It has numerous pivotal roles in different cellular processes including cell proliferation, differentiation, metabolism, phagocytosis, autophagy, and immune regulation 25 , 43 . Evidence has shown that ITPR1 could function as a direct novel target of hypoxia-inducible factor subunit 2 alpha ( HIF2α) involving in the activation of autophagy.…”

ITPR1-associated spinocerebellar ataxia with craniofacial features—additional evidence for germline mosaicism

“…It is thought to increase intracellular calcium levels by acting as an IP3-mediated calcium channel (Huang et al 2012;Berridge 1993;Hirota et al 2003). Although highly expressed in the Purkinje cells of the cerebellar vermis, ITPR1 has also been associated with sepsisassociated immuno-coagulation, autophagy in breast cancer, and apoptosis in bladder cancer (Furuichi et al 1993;Worley et al 1987;Zhang et al 2020;Tsunoda et al 2005;Han et al 2022).…”