A pretreatment ECM-high/immune-low transcriptomic score is associated with pathological complete response after neoadjuvant therapy in breast cancer
- 1Department of Thyroid and Breast Surgery, Hubei No. 3 People’s Hospital of Jianghan University, Wuhan, Hubei, China
- 2Department of Cardiothoracic, Thyroid and Breast Surgery, Enshi Central Hospital, Enshi, Hubei, China
Abstract
In this retrospective public-cohort observational study, we evaluated a biologically motivated extracellular matrix (ECM)-high/immune-low transcriptomic score for association with pathological complete response (pCR) after neoadjuvant therapy in breast cancer. The score contrasted standardized ECM/fibroblast and immune-response components. Cohort-specific logistic models adjusted for available clinical covariates; their performance was evaluated separately and was not validation of a locked transported model. In I-SPY2/GSE194040 (n = 987; 319 pCR events), a one-standard-deviation higher score was associated with lower pCR odds (odds ratio [OR] 0.687, 95% confidence interval [CI] 0.588–0.803). Inverse adjusted estimates were also observed in GSE25066 (OR 0.744, 95% CI 0.568–0.975) and GSE20271 (OR 0.407, 95% CI 0.232–0.715). Apparent areas under the receiver operating characteristic curve (AUCs) for these multivariable models were 0.750, 0.732 and 0.798; corresponding 500-bootstrap optimism-corrected estimates were 0.731, 0.713 and 0.765, conditional on processed scores. GSE20194 estimates were nonsignificant, and substantial record overlap with GSE25066 prevented interpretation as additional independent confirmation. A GSE25066 sensitivity restricted to deposited human epidermal growth factor receptor 2 (HER2)-negative status retained direction but had a confidence interval crossing unity. Higher scores correlated with lower immune-related reverse-phase protein array signals in matched I-SPY2 samples. The findings support a hypothesis-generating bulk-transcriptomic response association, with limited cross-cohort robustness. Heterogeneous treatment, sampling, assay and endpoint annotations, together with absent spatial and prospective validation, preclude claims of causality or clinical treatment-selection utility.
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BibTeX
@article{wang2026pretreatment,
title = {{A pretreatment ECM-high/immune-low transcriptomic score is associated with pathological complete response after neoadjuvant therapy in breast cancer}},
author = {Tao Wang and Xiaoyun Wu},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0357532},
url = {https://doi.org/10.1371/journal.pone.0357532},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A pretreatment ECM-high/immune-low transcriptomic score is associated with pathological complete response after neoadjuvant therapy in breast cancer
AU - Tao Wang
AU - Xiaoyun Wu
PY - 2026
DA - 2026/11/05
JO - PLOS One
DO - 10.1371/journal.pone.0357532
UR - https://doi.org/10.1371/journal.pone.0357532
AB - In this retrospective public-cohort observational study, we evaluated a biologically motivated extracellular matrix (ECM)-high/immune-low transcriptomic score for association with pathological complete response (pCR) after neoadjuvant therapy in breast cancer. The score contrasted standardized ECM/fibroblast and immune-response components. Cohort-specific logistic models adjusted for available clinical covariates; their performance was evaluated separately and was not validation of a locked transported model. In I-SPY2/GSE194040 (n = 987; 319 pCR events), a one-standard-deviation higher score was associated with lower pCR odds (odds ratio [OR] 0.687, 95% confidence interval [CI] 0.588–0.803). Inverse adjusted estimates were also observed in GSE25066 (OR 0.744, 95% CI 0.568–0.975) and GSE20271 (OR 0.407, 95% CI 0.232–0.715). Apparent areas under the receiver operating characteristic curve (AUCs) for these multivariable models were 0.750, 0.732 and 0.798; corresponding 500-bootstrap optimism-corrected estimates were 0.731, 0.713 and 0.765, conditional on processed scores. GSE20194 estimates were nonsignificant, and substantial record overlap with GSE25066 prevented interpretation as additional independent confirmation. A GSE25066 sensitivity restricted to deposited human epidermal growth factor receptor 2 (HER2)-negative status retained direction but had a confidence interval crossing unity. Higher scores correlated with lower immune-related reverse-phase protein array signals in matched I-SPY2 samples. The findings support a hypothesis-generating bulk-transcriptomic response association, with limited cross-cohort robustness. Heterogeneous treatment, sampling, assay and endpoint annotations, together with absent spatial and prospective validation, preclude claims of causality or clinical treatment-selection utility.
SN - 1932-6203
ER -