Computational dissection of the regulatory mechanisms of aberrant metabolism in remodeling the microenvironment of breast cancer
The composition of T cell subsets and tumor-specific T cell interactions within the tumor microenvironment(TME)contribute to the heterogeneity observed in breast cancer.Moreover,aberrant tumor metabolism is often intimately linked to dysregulated anti-tumor immune function of T cells.Identifying key metabolic genes that affect immune cell interactions thus holds promise for uncovering potential therapeutic targets in the treatment of breast cancer.This study leverages single-cell transcriptomic data from breast cancer to investigate tumor-specific T-cell subsets and their interacting subnetworks in the TME during cancer progression.We further assess the metabolic pathway activities of tumor-specifically activated T-cell subsets.The results reveal that metabolic pathways involved in insulin synthesis,secretion,degradation,as well as fructose catabolism,significantly influence multiple T cell interactions.By integrating the metabolic pathways that significantly up-regulate T cells in tumors and influence their interactions,we identify key abnormal metabolic genes associated with T-cell collaboration and further develop a breast cancer risk assessment model.Additionally,using gene expression profiles of prognosis-related genes significantly associated with aberrant metabolism and drug IC50 values,we predict targeted drugs,yielding potential candidates like GSK-J4 and PX-12.This study integrate the analysis of abnormal T-cell interactions and metabolic pathway abnormalities in the breast cancer TME,elucidating their roles in cancer progression and providing leads for novel breast cancer therapeutic strategies.
breast cancermicroenvironmental remodellingaberrant metabolismT-cell interactions
万方数据
维普
