Effect of Radiotherapy on Activating the Pyroptotic Cell Death Pathway in Breast Cancer Patients: The Role of Serum GSDMD-CT, NLRP3 and IL-18.

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most common form of cancer among women and the second leading cause of cancer-related death worldwide. Several malignancies can be successfully treated with radiation (RT), although radioresistance is still a major contributor to radiotherapy failure. Ionizing radiation (IR) induces pyroptosis in cancer cells. Pyroptosis is a designed method of death connected to routine immunity and directly related to the body ROS content. Objective for the study The aim of this work was to investigate the role of serum GSDMD-CT, nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) and IL-18 as predictors of pyroptotic cell death mechanism induced by radiotherapy in breast cancer patients. SUBJECTS AND METHODS: The 70 female participants in this study were divided into two groups Group (I) 40 breast cancer patients treated with radiotherapy. Group (II) a control group of 30 healthy volunteers with similar ages and sex. Patients with breast cancer received radiation, with a dose of 44 Gray administered over the course of 16 days in five daily fractions of 2.75 Gray each. Two blood samples were taken from breast cancer patients one before radiotherapy and the other after radiotherapy. While one blood sample was taken from healthy controls. The levels of the circulating pyroptosis biomarkers IL-18, NLRP3, and GSDMD-CT were measured using the ELISA method. RESULTS: Our results showed that, there was a significant increase in serum pyroptosis markers GSDMD-CT, NLRP3 and IL-18 in BC Patients after RT when compared to before radiotherapy. CONCLUSION: Radiotherapy induced pyroptosis in breast cancer patients as a new cell death mechanism. GSDMD-CT, NLRP3 and IL-18 are biomarkers of pyroptosis that significantly increased post irradiation highlighting enhanced ROS and pyroptosis induction.