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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1695689

This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 22 articles

Multi-scale data reveal a CD24(+) MUCL1(+) tumor subgroup associated with unfavorable prognosis in ER+ breast cancer

Provisionally accepted
Yingxi  LiYingxi Li1Junming  CaoJunming Cao2Hai  LinyueHai Linyue2Jing  ZengJing Zeng3Dongchen  TianDongchen Tian2Yue  YuYue Yu2*Zhaohui  ChenZhaohui Chen2*Yao  TianYao Tian2,3*
  • 1Ningbo University Health Science Center, Ningbo, China
  • 2Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
  • 3Ningbo Medical Centre Lihuili Hospital, Ningbo, China

The final, formatted version of the article will be published soon.

Objective: Breast cancer remains the leading cause of cancer-associated death for females globally. For the group of ER+ breast cancer patients, there are still some problems of poor prognosis that need to be solved. This study aims to identify the poor prognostic tumor subgroups for prognostic stratification of ER+ patients. Methods: Through a comprehensive multi-omics strategy, we systematically characterized the biological and clinical significance of MUCL1+CD24+ cells in breast cancer. And we used multiplex immunohistochemistry to confirmed the poor role of MUCL1+CD24+ cells. Results: Single-cell transcriptomics unraveled the cellular ontogeny and immune microenvironment interactions of this subset, while bulk RNA sequencing exposed significant pathway heterogeneity and differential immunotherapy responses associated with varying cellular abundance levels. Genomic landscape analysis pinpointed specific somatic mutations correlated with MUCL1(+) CD24(+) cell infiltration patterns, findings that were subsequently validated through multiplex immunohistochemistry demonstrating strong prognostic value. Crucially, we developed a clinically translatable radiomics approach that successfully correlated specific MRI features with cellular prevalence, establishing a foundation for noninvasive detection of this aggressive cellular subpopulation. Conclusions: This integrative approach, spanning molecular to imaging analyses, provides novel insights into both the biological drivers and clinical implications of MUCL1(+) CD24(+) cells in breast cancer progression.

Keywords: ER+ breast cancer, MUCL1(+) CD24(+) cells, Tumor Microenvironment, Radiomics, single-cell RNA sequencing

Received: 30 Aug 2025; Accepted: 26 Sep 2025.

Copyright: © 2025 Li, Cao, Linyue, Zeng, Tian, Yu, Chen and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yue Yu, yuyue@tmu.edu.cn
Zhaohui Chen, chenzhaohui2021@tmu.edu.cn
Yao Tian, tianyao@tmu.edu.cn

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