Comprehensive evaluation of cell death-related genes as novel diagnostic biomarkers for breast cancer

Background: Breast cancer (BRCA) ranks first among cancers in terms of incidence and mortality rates in women, primarily owing to metastasis, chemo-resistance, and heterogeneity. To predict long-term prognosis and design novel therapies for BRCA, more sensitive markers need to be explored. Methods: Data from 1089 BRCA patients were downloaded from TCGA database. Pearson's correlation analysis and univariate and multivariate Cox regression analyses were performed to assess the role of cell death-related genes (CDGs) in predicting BRCA prognosis. Kaplan-Meier survival curves were generated to compare the overall survival in the two subgroups. A nomogram was constructed using risk scores based on the five CDGs and other clinicopathological features. CCK-8, EdU incorporation, and colony formation assays were performed to verify the inhibitory effect of NFKBIA on BRCA cell proliferation. Transwell assay, flow cytometry, and immunohistochemistry analyses were performed to ascertain the biological function of NFKBIA. Results: Five differentially expressed CDGs were detected among 156 CDGs. The risk score for each patient was then calculated based on the expression levels of the five CDGs. Distinct differences in immune infiltration, expression of immune-oncological targets, mutation status, and half-maximal inhibitory concentration values of some targeted drugs were observed between the high- and low-risk groups. Finally, in vitro cell experiments verified that NFKBIA overexpression suppresses the proliferation and migration of BRCA cells. Conclusions: Our study revealed that some CDGs, especially NFKBIA, could serve as sensitive markers for predicting the prognosis of patients with BRCA and designing more personalized clinical therapies.