Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026
Spatial transcriptome revealed associated biomarkers for endocrine therapy response in HR-positive/HER2-negative early breast cancer.
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Tan Yujing, Wang Jiani, Chen Zhe, Lin Shengbo, Zeng Cheng, Zhu Lin, Wang Yufei, Qian Haili, Xu Binghe, Fan Ying, Ma Fei
Аннотация
OBJECTIVE: Endocrine resistance occurs in nearly all patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), which can develop local and distant recurrence. The situation highlights the need to explore biomarkers for the efficacy of endocrine therapy (ET).
METHODS: We performed digital spatial profiling on postoperative tumor samples from 20 HR+/HER2- EBC patients receiving adjuvant tamoxifen therapy, based on a designated panel comprising 235 ET-related genes. Paired patients were stratified into resistant and sensitive groups based on ET response. A total of 111 regions in three tissue compartments defined by morphology markers [tumor (PANCK+), leucocytes (CD45+), and nonimmune stroma (CD45-/PANCK-)] were investigated for immune and transcriptomic biomarkers.
RESULTS: A total of 27, 13, and 5 differentially expressed genes (DEGs) were identified in PANCK+, CD45+, and CD45-/PANCK- regions. In the PANCK+ regions, mRNA expression of fourteen DEGs was significantly associated with disease-free survival (DFS), among which seven DEGs were further selected to construct a model for DFS. In the model, patients with low-risk scores had a median DFS of 55.77 months, significantly longer than 21.67 months among those with high-risk scores [P=2.1e-4, hazard ratio (HR)=6.73, 95% confidence interval (95% CI) =2.20-20.60)]. The area under curve for 1-year, 3-year, and 5-year DFS was 0.98, 0.95, and 0.91, indicating its superior efficacy. ET-sensitive patients had significantly higher non-classical monocyte infiltration in the CD45+ regions (P=0.03), whereas ET-resistant patients had significantly higher plasma cell infiltration in the CD45-/PANCK- regions (P=0.01).
CONCLUSIONS: Our study has first demonstrated the spatial transcriptomic landscapes of patients with different responses to ET, which may help stratify patients who are responsive to ET and motivate the exploration of the molecular mechanisms of endocrine resistance.
METHODS: We performed digital spatial profiling on postoperative tumor samples from 20 HR+/HER2- EBC patients receiving adjuvant tamoxifen therapy, based on a designated panel comprising 235 ET-related genes. Paired patients were stratified into resistant and sensitive groups based on ET response. A total of 111 regions in three tissue compartments defined by morphology markers [tumor (PANCK+), leucocytes (CD45+), and nonimmune stroma (CD45-/PANCK-)] were investigated for immune and transcriptomic biomarkers.
RESULTS: A total of 27, 13, and 5 differentially expressed genes (DEGs) were identified in PANCK+, CD45+, and CD45-/PANCK- regions. In the PANCK+ regions, mRNA expression of fourteen DEGs was significantly associated with disease-free survival (DFS), among which seven DEGs were further selected to construct a model for DFS. In the model, patients with low-risk scores had a median DFS of 55.77 months, significantly longer than 21.67 months among those with high-risk scores [P=2.1e-4, hazard ratio (HR)=6.73, 95% confidence interval (95% CI) =2.20-20.60)]. The area under curve for 1-year, 3-year, and 5-year DFS was 0.98, 0.95, and 0.91, indicating its superior efficacy. ET-sensitive patients had significantly higher non-classical monocyte infiltration in the CD45+ regions (P=0.03), whereas ET-resistant patients had significantly higher plasma cell infiltration in the CD45-/PANCK- regions (P=0.01).
CONCLUSIONS: Our study has first demonstrated the spatial transcriptomic landscapes of patients with different responses to ET, which may help stratify patients who are responsive to ET and motivate the exploration of the molecular mechanisms of endocrine resistance.