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.