Cancer-testis antigens as potential targets for the development of therapeutic strategies for breast cancer

Introduction: Breast cancer is the most prevalent malignancy among women worldwide, corresponding to an age-adjusted incidence rate of 41.89 cases per 100,000 women.In recent years, breast cancer surpassed lung cancer as the most frequently diagnosed cancer globally.Immunotherapy has revolutionized cancer treatment, primarily through monoclonal antibodies targeting immune checkpoints.Despite significant success, its efficacy is limited to 20-40% of patients, depending on tumor type.Objectives: To overcome this limitation, we are developing a novel approach to identify target molecules for vaccine-based breast cancer immunotherapy.Cancer/Testis Antigens (CTAs) constitute a class of highly immunogenic proteins typically restricted to gametogenic tissues but aberrantly expressed in various malignancies, making them compelling candidates for cancer vaccine development. Methodology:In this study, RNA-seq data from ductal and lobular breast cancer samples, along with their matched adjacent normal tissues, were retrieved from The Cancer Genome Atlas (TCGA) database.A total of 341 genomic regions annotated as testis antigens were compiled from the National Center for Biotechnology Information (NCBI) and University of California, Santa Cruz (UCSC) databases.Transcriptomic reads were aligned to the human reference genome, enabling the mapping and quantification of CTA expression levels.Results: Differential expression analysis between tumor and normal breast tissues revealed eight CTAs significantly overexpressed in breast cancer samples.To further validate these findings, confirmatory analyses were performed using independent datasets from the GEPIA, UALCAN, and Human Protein Atlas (HPA) platforms. Conclusion:These complementary assessments reinforced the robustness of our results regarding CTA differential expression in breast tumors.These results support the potential of CTAs as immunotherapeutic targets, paving the way for vaccine-based strategies that could offer more precise and less toxic alternatives to conventional treatments.