ArticleBreast cancer (Tokyo, Japan)2026
Identifying breast cancer subtypes and exploring spatial expression patterns of the key subtype-specific gene based on pathological images, single-cell sequencing, and spatial transcriptomic data.
Article in Breast cancer (Tokyo, Japan), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBreast cancer (BRCA) is a heterogeneous disease. Accurate prognosis and molecular subtypes are critical for personalized treatment in BRCA. This study aimed to identify prognostic subtypes of BRCA based on features derived from pathological images and to explore their potential molecular and cellular mechanisms using spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq).
methodsHematoxylin and eosin (H&E)-stained images were obtained from the TCGA-BRCA dataset using the OTSU algorithm. Pathological features were extracted using PyRadiomics. Feature selection was performed via Cox regression and machine learning. Subtypes were defined through consensus clustering, followed by differential gene expression. Key genes were identified using WGCNA and Lasso regression analysis. The spatial distribution and cellular interactions of key genes were analyzed by integrating ST and scRNA-seq datasets.
resultsAmong 1,406 extracted pathological features, 25 core features were identified, based on which two BRCA subtypes were defined. The C1 subtype was associated with advanced disease and poor prognosis. ESRP1 was identified as a key gene upregulated in the C1 subtype. ST analysis revealed that ESRP1 was highly expressed in tumor lesion areas and co-localized with epithelial and fibroblast cells. Cell-cell communication analysis revealed that fibroblasts served as central hubs in the TGF-β signaling network, particularly in regions enriched with ESRP1.
conclusionsThis study identified pathology-derived prognostic BRCA subtypes that complement existing molecular classifications. The core gene, ESRP1, exhibited distinct spatial expression patterns in BRCA tissues, primarily localized to tumor core regions enriched with fibroblast cells. These findings provide exploratory insights into BRCA heterogeneity and potential therapeutic targets.
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