Project description:Oxysterols, oxidized derivatives of cholesterol, act in breast cancer (BC) as selective estrogen receptor modulators and affect cholesterol homeostasis, drug transport, nuclear and cell receptors, and other signaling proteins. Using overlapping data from patients with early-stage estrogen receptor-positive BC—high-coverage targeted DNA sequencing (99 patients, 113 genes), mRNA sequencing (67 patients), and full miRNome by microarrays (123 patients)—we describe complex mRNA-miRNA and miRNA-miRNA interaction (correlation) networks, with validation in two carefully curated public datasets (n=538 in total) and 11 databases. The ESR1-CH25H-INSIG1-ABCA9 axis was the most prominent, being interconnected through hsa-miR-125b-5p, but also hsa-miR-99a-5p, hsa-miR-100-5p, hsa miR 143 3p, hsa-199b-5p, hsa-miR-376a-3p, and hsa-miR-376c-3p. Mutations in SC5D, CYP46A1, and its functionally linked gene set were associated with multiple differentially expressed genes. STARD5 was upregulated in patients with positive lymph node status. High expression of miR-19b-3p was weakly associated with poor survival in multiple datasets. This is the first detailed dedicated study of interactions between DNA variation and mRNA expression of oxysterol-related genes, the miRNA transcriptome, and clinical factors in BC.
Project description:BackgroundBreast cancer is a heterogeneous malignant disease with a varying prognosis and is classified into four molecular subtypes. It remains one of the most prevalent cancers globally, with the tumor microenvironment playing a critical role in disease progression and patient outcomes.MethodsThis study evaluated tumor samples from 40 female patients with luminal A and B breast cancer, utilizing flow cytometry to phenotypically characterize the immune cells and tumor cells present within the tumor tissue.ResultsThe luminal B-like tumor samples exhibited increased infiltration of CD4+ cells, regulatory T cells (Tregs), and Th17 cells and decreased levels of NK cells, γδ T cells, Th1 cells, and follicular T cells, which is indicative of a more immunosuppressive tumor microenvironment.ConclusionsThese findings suggest that luminal B-like tumors have a microenvironment that is less supportive of effective anti-tumor immune responses compared to luminal A tumors. This study enhances the understanding of the immunological differences between luminal subtypes of breast cancer and identifies potential new therapeutic targets and biomarkers that could drive advancements in precision medicine for breast cancer management.
