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Single-cell transcriptomic profiling reveals a KRT17-enriched EMT-like epithelial state associated with T/NK cell dysfunction in breast cancer
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DOI：10.1007/s12672-026-05712-8.png)
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Abstract
En 中文
Epithelial plasticity is increasingly recognized as a key feature of breast cancer progression, but its relationship with antitumor immune dysfunction remains insufficiently characterized. To investigate this issue, we integrated single cell transcriptomic profiles from human breast tissues with bulk transcriptomic and survival data from breast cancer cohorts. Through reanalysis of the epithelial compartment, we identified a distinct KRT17 enriched epithelial population, designated Epi_C7_KRT17, that displayed prominent epithelial to mesenchymal transition programs, elevated CytoTRACE2 inferred plasticity, and enhanced activity of EMT associated regulatory circuits, including the FOSL1 regulon. Trajectory analysis placed this population along an epithelial state transition continuum in which EMT related genes were progressively induced, suggesting that Epi_C7_KRT17 represents a plastic epithelial state rather than a subset defined only by marker expression. Clinically, a gene signature derived from Epi_C7_KRT17 was associated with unfavorable overall survival, supporting its prognostic relevance. Further immune profiling revealed that tumors with high Epi_C7_KRT17 abundance contained fewer CD8 T cell and natural killer cell populations and showed broadly attenuated immune effector programs, including cytotoxicity, activation, T cell receptor signaling, and interferon response signatures. Intercellular communication analysis further suggested that KRT17 enriched epithelial cells may participate in reshaping epithelial and immune cell crosstalk, with MIF related signaling emerging as a prominent interaction axis involving T and NK cell populations. Collectively, this study identifies a KRT17 enriched EMT associated epithelial state associated with epithelial plasticity, weakened T and NK cell activity, and poor clinical outcome in breast cancer. These findings provide a framework informed by single cell analysis for understanding how malignant epithelial state transitions may be coupled to immune microenvironment remodeling.
Keywords:
Breast cancer
Single-cell RNA sequencing
KRT17
Epithelial–mesenchymal transition
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