Identification of Shared Target Genes for Breast and Colorectal Cancer: A Mendelian Randomization and Spatial Transcriptomics Analysis

Introduction: Breast and colorectal cancers are major global health burdens, with breast cancer being one of the most prevalent cancers worldwide and colorectal cancer ranking third in incidence and second in cancer-related mortality. Central memory T (TCM) cells, a subset of CD8 + T cells, play a crucial role in tumor immunity and are promising targets for immunotherapy. Identifying common signaling molecules in TCM cells across these two cancer types could enhance our understanding of tumor progression and contribute to the development of therapeutic strategies applicable to both cancers. Materials and Methods Single-cell RNA sequencing (scRNA-seq) data for breast cancer (GSE161529) and colorectal cancer (GSE222300) were retrieved from the GEO database. Data normalization, dimensionality reduction, and identification of T cell subsets were performed. Differential gene expression analysis focused on central memory CD8 + T cells. Mendelian randomization (MR), reverse causality detection, and co-localization analyses were employed to explore the associations between differentially expressed genes and disease risk. Pseudotime and metabolic analyses, along with spatial transcriptomics, were used to evaluate gene expression patterns and metabolic pathways. Protein-protein interaction (PPI) analysis assessed the interactions between drug target genes. Results We identified four genes (ZFP36L2, CKS1B, PTTG1, and ITGAE) that are associated with the risk of both breast and colorectal cancer. Pseudotime analysis revealed that the expression levels of CKS1B and PTTG1 decreased over time (P < 0.05), while ZFP36L2 and ITGAE expression increased (P < 0.05). Metabolic pathway analysis indicated that these genes were significantly involved in cysteine and methionine metabolism, with spatial transcriptomics corroborating these findings. Furthermore, PPI analysis highlighted a potential interaction between PTTG1 and CKS1B. Conclusion This study highlights the potential roles of ZFP36L2, CKS1B, PTTG1, and ITGAE in the development of breast and colorectal cancers through their influence on central memory CD8 + T cells. These genes may serve as shared biomarkers for diagnosis, therapeutic targeting, and monitoring therapeutic response across both cancers.