Research Article: Immunogenic Cell Death-Related Gene Expression Signatures in Breast Cancer Subtypes: A TCGA- and GEO-Based Analysis with Potential Therapeutic Implications.

Immunogenic cell death (ICD) is a regulated form of cell death that elicits an adaptive immune response, recognized as a promising strategy in cancer immunotherapy. Its therapeutic efficacy, however, can be influenced by tumor-intrinsic factors, particularly in heterogeneous diseases like breast cancer (BC). This study investigated the ICD-related gene expression signature in BC using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohorts. Analysis revealed significantly elevated expression of HSP90AA1, CXCR3, MYD88, FOXP3, PDIA3, XBP1, and IFNB1, and reduced expression of P2RX7 in BC tissues compared with normal tissues. Furthermore, the expression of these genes varied significantly across distinct BC subtypes, patient ages, and tumor stages. Concurrently, an investigation into the UPR pathway, known to intersect with ICD, highlighted Binding immunoglobulin Protein (BiP/GRP78/HSPA5) as a molecule of interest. To explore potential modulators of this pathway, in silico docking studies were performed, which predicted favorable binding interactions of quercetin and taxifolin with BiP. These findings suggest that characterizing the expression patterns of these ICD-related genes and UPR components could inform the development of personalized immunotherapeutic strategies for BC, tailored to specific tumor subtypes, stages, and patient demographics. Further exploration of BiP's role and its potential for therapeutic manipulation may offer novel avenues to enhance anti-tumor immunity.