Lactylation-related gene signature for prognostic prediction and immune infiltration analysis in breast cancer.

Background: Lactylation is implicated in various aspects of tumor biology, but its relation to breast cancer remains poorly understood. This study aimed to explore the roles of the lactylation-related genes in breast cancer and its association with the tumor microenvironment. Methods: The expression and mutation patterns of lactylation-related genes were analyzed using the breast cancer data from The Cancer Genome Atlas (TCGA) database and GSE20685 datasets. Unsupervised clustering was used to identify two lactylation clusters. A lactylation-related gene signature was developed and validated using the training and validation cohorts. Immune cell infiltration and drug response were assessed. Results: We analyzed the mRNA expression, copy number variations, somatic mutations, and correlation networks of 22 lactylation-related genes in breast cancer tissues. We identified two distinct lactylation clusters with different survival outcomes and immune microenvironments. We further classified the patients into two gene subtypes based on lactylation clusters and identified a 7-gene signature for breast cancer survival prognosis. The prognostic score based on this signature demonstrated prognostic value and predicted the therapeutic response. Conclusion: Lactylation-related genes play a critical role in breast cancer by influencing tumor growth, immune microenvironment, and drug response. This lactylation-related gene signature may serve as a prognostic marker and a potential therapeutic target for breast cancer.

MGP+ and IDO1+ tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing.

Immunotherapy is widely applied for the treatment of breast cancer, but to which some patients respond poorly or develop resistance. Therefore, the mechanism needs to be further studied. Transcriptomic data of 31 breast cancer patients treated with anti-programmed death receptor 1 (PD-1) was downloaded from the VIB-KULeuven Center for Cancer Biology to analyze the changes in myeloid cells in tumor tissues before and after immunotherapy. And 24 cell populations that may be immune-related were further identified. Representative cell populations were also screened and validated through cellular and animal experiments to evaluate the relevant molecular expression and pathways of tumor-associated macrophages (TAMs) in the tumor microenvironment. The results demonstrated that MGP+ TAMs and IDO1+ TAMs influenced the efficacy of immunotherapy in breast cancer patients. After anti-PD-1 treatment, Increased numbers of MGP+ TAMs and IDO1+ TAMs in breast cancer patients upregulated pro-tumorigenic factors associated with resistance to immunosuppressive therapy. This study provides new biomarkers for immunotherapy to predict therapeutic responses and overcome potential resistance to immunotherapy. It is an important complement to the immunosuppression caused by TAMs after immunotherapy for breast cancer.