Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Tumor microenvironment transcriptional activity enables robust stratification of chemotherapy response in triple-negative breast cancer

Dai, Yaoyi ; Pan, Xiaoxi ; Guo, Shuai ; Ji, Shuangxi ; Cao, Shaolong ; Montierth, Matthew D ; Jiang, Yujie ; Chang, Jeffrey T ; Shi, Leming and Shalapour, Shabnam , et al. (2026) In Cell Reports Medicine 7(2). p.1-15
Abstract

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features... (More)

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven proliferation programs, and low-TmS tumors display immune dysfunction with memory B cell enrichment and divergent RAS/mitogen-activated protein kinase (MAPK) activation, compared to Western populations. Despite these differences, extracellular matrix organization represents a conserved therapeutic vulnerability in treatment-resistant low-TmS patients. TmS provides a unifying framework for dissecting TNBC heterogeneity and enabling precision therapy across diverse populations.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Triple Negative Breast Neoplasms/genetics, Female, Tumor Microenvironment/genetics, Gene Expression Regulation, Neoplastic, Prognosis, Drug Resistance, Neoplasm/genetics, Transcription, Genetic, RNA, Messenger/genetics
in
Cell Reports Medicine
volume
7
issue
2
article number
102610
pages
1 - 15
publisher
Cell Press
external identifiers
  • scopus:105030535338
  • pmid:41707645
ISSN
2666-3791
DOI
10.1016/j.xcrm.2026.102610
language
English
LU publication?
yes
additional info
Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.
id
fe77a589-e7ea-46c5-a484-8f2587c52a48
date added to LUP
2026-02-20 12:50:44
date last changed
2026-05-07 14:47:26
@article{fe77a589-e7ea-46c5-a484-8f2587c52a48,
  abstract     = {{<p>Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven proliferation programs, and low-TmS tumors display immune dysfunction with memory B cell enrichment and divergent RAS/mitogen-activated protein kinase (MAPK) activation, compared to Western populations. Despite these differences, extracellular matrix organization represents a conserved therapeutic vulnerability in treatment-resistant low-TmS patients. TmS provides a unifying framework for dissecting TNBC heterogeneity and enabling precision therapy across diverse populations.</p>}},
  author       = {{Dai, Yaoyi and Pan, Xiaoxi and Guo, Shuai and Ji, Shuangxi and Cao, Shaolong and Montierth, Matthew D and Jiang, Yujie and Chang, Jeffrey T and Shi, Leming and Shalapour, Shabnam and Echeverria, Gloria V and Yates, Lucy and Staaf, Johan and Lim, Bora and Yuan, Yinyin and Wang, Wenyi}},
  issn         = {{2666-3791}},
  keywords     = {{Humans; Triple Negative Breast Neoplasms/genetics; Female; Tumor Microenvironment/genetics; Gene Expression Regulation, Neoplastic; Prognosis; Drug Resistance, Neoplasm/genetics; Transcription, Genetic; RNA, Messenger/genetics}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{1--15}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports Medicine}},
  title        = {{Tumor microenvironment transcriptional activity enables robust stratification of chemotherapy response in triple-negative breast cancer}},
  url          = {{http://dx.doi.org/10.1016/j.xcrm.2026.102610}},
  doi          = {{10.1016/j.xcrm.2026.102610}},
  volume       = {{7}},
  year         = {{2026}},
}