The effects of Stim1 and Orai1 expression levels on lymph node metastases and prognosis in patients with triple negative breast cancer

Abstract

Objective: Calcium signaling pathways are closely related to breast cancer, including Calcium ions (Ca²⁺) metabolic disorders associated with cell proliferation and migration of triple-negative breast cancer (TNBC). The key proteins of store-operated Ca²⁺ entry (SOCE), Stromal interaction molecule 1 (Stim1) and calcium release-activated calcium channel protein1(Orai1), play critical roles in the development of TNBC. Method: Fifty cases of TNBC patients who had treatment in our hospital between January 2011 and January 2016 were included in the study, including no lymph node (LN) metastasis(N=20), 1-3 LNs metastasis(N=20) and ≥4 LNs metastasis(N=10). The para-cancerous tissues of TNBC patients and the plasma of healthy patients (N=20) were used as control groups for tumor tissue and plasma samples of TNBC patients, respectively. Real-time reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) were used to detect Stim1, Orai1 in the aforementioned tissue and plasma samples, respectively. Meantime, we used the Kaplan Meier (K-M) method to analyze the relationship between the expression levels of Stim1 and Orai1 and the prognosis of TNBC patients. Finally, the expression of SOCE and its key proteins (Stim1 and Orai1) in TNBC patients was analyzed using the TCGA database. Main results: In TNBC patients, the expression of Stim1 and Orai1 were higher than in the control group (P>0.05). Besides, TNBC patients without LN metastases had higher Orai1 gene expression levels than the group with LN metastasis (P<0.05). The prognosis of TNBC patients is worse when the Orai1 expression is lower (P>0.05). Furthermore, TNBC patients with a tumor diameter≥5cm have a higher degree of axillary LN metastasis and poorer prognosis compared to patients with a diameter＜5cm. On the contrary, bioinformatics analysis showed that the key protein Stim1 of SOCE was downregulated in TNBC patients and negatively correlated with the degree of lymph node metastasis, which is a protective factor in TNBC patients. Conclusion: Orai1 is expected to be tumor markers in the field of TNBC. In addition, the Orai1 expression level and tumor diameter could be used to predict the TNBC axillary LN metastatic status and prognostic level. The relationship between Stim1 and the degree of TNBC lymph node metastasis needs further research.