MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy

作者：Gaofeng Ni, Yuwei Sun, Hongling Jia, Zhikai Xiahou, Yumeng Li, Fu Zhao, Hongyan Zang · 发表于：Translational Oncology · 年份：2025 · DOI：10.1016/j.tranon.2025.102280 · 被引用次数：23 · 研究领域：Hippo pathway signaling and YAP/TAZ、Melanoma and MAPK Pathways、Cancer Immunotherapy and Biomarkers

BACKGROUND: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment. Understanding the molecular mechanisms behind this resistance, including tumor heterogeneity and changes in the tumor microenvironment, was crucial for overcoming resistance, identifying new therapeutic targets, and developing more effective personalized treatments. METHODS: The study utilized single-cell RNA sequencing (scRNA-seq) data sourced from the Gene Expression Omnibus database and The Cancer Genome Atlas to analyze HR+BC and identify key cellular characteristics. Cell type identification was achieved through Seurat's analytical tools, and subtype differentiation trajectories were inferred using Slingshot. Cellular communication dynamics between tumor cell subtypes and other cells were analyzed with the CellChat. The pySCENIC package was utilized to analyze transcription factors regulatory networks in the identified tumor cell subtypes. The results were verified by in vitro experiments. A risk scoring model was developed to assess patient outcomes. RESULTS: This study employed scRNA-seq to conduct a comprehensive analysis of HR+BC tumor subtypes, identi...