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Peer-reviewedCC BY-NC-NDCancer medicine

Integrated Spatial and Bulk Transcriptomic Analysis Identifies a Multicellular Ecosystem Involved in Progression of Young Breast Cancer.

  • Xiaolin Chen1,2
  • Zhuozhi Liang1,2,3
  • Xinming Chen4,5
  • Qian Ouyang1,2
  • Qianru Chen1,2
  • Liling Zhu1,2,5
  • Shunrong Li6
  • Kai Chen2,4,5
6 affiliations
  1. 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  2. 2Guangdong Provincial Clinical Research Center for Breast Diseases, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  3. 3Zenith Institute of Medical Sciences, Guangzhou, Guangdong, China.
  4. 4Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei, Guangdong, China.
  5. 5Department of Breast Surgery, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei, Guangdong, China.
  6. 6Department of General Surgery (Breast Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
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Abstract

Young breast cancer (YBC), defined as diagnosis at or before the age of 40 years, is characterized by an aggressive phenotype and poor prognosis. The tumor microenvironment (TME), comprising immune and stromal cells, plays a critical role in tumor initiation and progression and is closely associated with clinical outcomes. However, alterations in cell states and the organization of multicellular ecosystems within the YBC microenvironment remain poorly understood. We analyzed 7379 bulk transcriptome samples and spatial transcriptomic data from eight samples using EcoTyper and complementary spatial analyses. The abundance of CD4+ T cells (S07), fibroblasts (S05), monocytes/macrophages (S09), and epithelial cells (S05) was significantly lower in young than in older patients with breast cancer. CD4+ T cells (S07), fibroblasts (S05), and monocytes/macrophages (S09) formed a spatially organized multicellular ecosystem with putative interactions involving CDH1-PTPRF/ERBB3. Lower ecosystem abundance was associated with poorer prognosis, including among patients who did not achieve a pathological complete response after neoadjuvant therapy. These findings identify a distinct multicellular ecosystem within the YBC microenvironment, providing insights into the microenvironmental features associated with disease progression.

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Cite

BibTeXRIS
BibTeX
@article{chen2026integrated,
  title = {{Integrated Spatial and Bulk Transcriptomic Analysis Identifies a Multicellular Ecosystem Involved in Progression of Young Breast Cancer.}},
  author = {Xiaolin Chen and Zhuozhi Liang and Xinming Chen and Qian Ouyang and Qianru Chen and Liling Zhu and Shunrong Li and Kai Chen},
  journal = {Cancer medicine},
  year = {2026},
  month = oct,
  doi = {10.1002/cam4.72367},
  url = {https://europepmc.org/article/MED/42897436},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Integrated Spatial and Bulk Transcriptomic Analysis Identifies a Multicellular Ecosystem Involved in Progression of Young Breast Cancer.
AU  - Xiaolin Chen
AU  - Zhuozhi Liang
AU  - Xinming Chen
AU  - Qian Ouyang
AU  - Qianru Chen
AU  - Liling Zhu
AU  - Shunrong Li
AU  - Kai Chen
PY  - 2026
DA  - 2026/10/01
JO  - Cancer medicine
DO  - 10.1002/cam4.72367
UR  - https://europepmc.org/article/MED/42897436
AB  - Young breast cancer (YBC), defined as diagnosis at or before the age of 40 years, is characterized by an aggressive phenotype and poor prognosis. The tumor microenvironment (TME), comprising immune and stromal cells, plays a critical role in tumor initiation and progression and is closely associated with clinical outcomes. However, alterations in cell states and the organization of multicellular ecosystems within the YBC microenvironment remain poorly understood. We analyzed 7379 bulk transcriptome samples and spatial transcriptomic data from eight samples using EcoTyper and complementary spatial analyses. The abundance of CD4+ T cells (S07), fibroblasts (S05), monocytes/macrophages (S09), and epithelial cells (S05) was significantly lower in young than in older patients with breast cancer. CD4+ T cells (S07), fibroblasts (S05), and monocytes/macrophages (S09) formed a spatially organized multicellular ecosystem with putative interactions involving CDH1-PTPRF/ERBB3. Lower ecosystem abundance was associated with poorer prognosis, including among patients who did not achieve a pathological complete response after neoadjuvant therapy. These findings identify a distinct multicellular ecosystem within the YBC microenvironment, providing insights into the microenvironmental features associated with disease progression.
SN  - 2045-7634
ER  -