The interplay between NLRP3 and S1P in Egyptian Metastatic and Non- Metastatic Breast Cancer Patients and their potential diagnostic implications

Abstract

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer and is considered the main cause of death in women worldwide. Metastatic BC is a state when cancerous cells spread to other tissues, including lung, bone, liver and brain. Sphingosine 1-phosphate (S1P) is emerging as a key regulator of proliferation, inflammation, vasculogenesis and resistance to apoptotic cell death. There is increasing evidence of a role of S1P receptors [e.g. sphingosine phosphate 4 (S1P4) and sphingosine kinase 1 (SK1)] in cancer, where overexpression of these proteins in estrogen receptor (ER) negative BC patients is linked to aggressive disease and poor prognosis. It has been discovered that the bioactive lipid metabolite S1P can act as a damage-associated molecular patterns (DAMP), and in vitro, it induced Nod-like receptor 3 (NLRP3) dependent activation of caspase-1 and secretion of interleukin-1b (IL-1b). Objective evaluate serum levels of S1P and NLRP3 to clarify the role of these markers in metastatic and non-metastatic BC patients and examine their potential as reliable novel diagnostic biomarkers. Methods The study involved 26 Egyptian female patients diagnosed with metastatic BC (stage 4) and 30 Egyptian female patient diagnosed with non-metastatic BC (stages 0, 1, 2 and 3). NLRP3, S1P and cancer antigen15.3 (CA 15.3) serum levels were analyzed using ELISA technique. Results The results revealed significantly lower serum levels of NLRP3 and S1P in non-metastatic and metastatic BC Egyptian patients compared to the healthy Egyptian female-control group (P < 0.001). ROC curve analysis showed that S1P has a promising good diagnostic utility in late-stage BC while NLRP3 has a moderate diagnostic utility in early and late BC. Conclusion NLRP3 and S1P could be promising novel diagnostic biomarkers of BC.