Calcium induces death is associated with Pyroptosis and the anti-tumor immunity in breast cancer

Abstract Background: Calcium (Ca2+) binds to the intracellular receptor calmodulin (CALM) as an intracellular messenger， Activates multiple downstream signalling pathways. In addition, previous studies report that the Ca2+/CAMK（calcium/calmodulin-dependent protein kinase） family plays an essential part in metabolic homeostasis. However, few studies have systematically analyzed the parts of the CALM and CAMK families in cancer. Therefore, CALMs/CAMKs were examined to determine their molecular characteristics and potential clinical significance in pan-cancer and to validate the connection between CAMK4 and pyroptosis of breast cancer cells.Methods: We downloaded the data from public databases, including cBioPortal for Cancer Genomics, GSCALite tool, UALCAN databases and Human Protein Atlas (HPA). Based on the Kaplan-Meier plotter platform, bc-GenExMiner and R 4.2.0, DRUGSURV database, prognosis in BRCA was analyzed. Individual CAMK4 and Pyroptosis related genes were respectively enriched on different pathways and biological processes via the GeneMANIA. Additionally, based on the TIMER, UCSC Xena, and TISIDB databases, we evaluated the relationship between CAMK4 and the immune microenvironment. GSCALite tool and CMap database were applied to predict small molecule compounds. Results: The different expression patterns of CALMs and CALMKs may be related to the different frequencies of genetic mutations, and these genes were involved in tumorigenesis pathways, which were closely connected to the prognosis of breast cancer. Furthermore， upregulation of CAMK4 expression correlated with progression of the tumor for patients with BRCA. CAMK4 and PRGs were connected with the tumor immune infiltration status of BRCA, which co-enriched genes can predict small molecule compounds for breast cancer treatment, such as ELAVL1, fasudil, ADC, PTPN1, etc.Conclusions: In breast cancer, the prolonged prognosis caused by upregulation of CAMK4 expression was assessed to be due to high immune infiltration. CAMK4 and PRGs co-regulate the tumor immune infiltration status of BRCA, which can be used as an intervention target for breast cancer anti-tumor immunotherapy.