Inflammatory breast cancer microenvironment repertoire based on DNA methylation data deconvolution reveals actionable targets to enhance the treatment efficacy

Sep 21, 2026

Uploaded by Oliver

Inflammatory breast cancer (IBC) mimics acute inflammation, yet the contribution of infiltrating immune and stromal cells remains unclear. The study investigates how tumor microenvironment (TME) components acquire molecular alterations, including epimutations, before overt morphological changes. Global DNA methylation profiling of IBC and surrounding tissues estimates microenvironment cellular composition and pinpoints epigenetically dysregulated markers linked to prognosis and therapy response.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Clinical features and standard trimodal treatment approach

Limitations of prior transcriptomic studies

Tumor microenvironment as a dynamic tumor-stroma interface

Calanca etal. Journal of Translational Medicine (2024) 22:735 [https://doi.org/10.1186/s12967-024-05553-5](https://doi.org/10.1186/s12967-024-05553-5) Journal of Translational Medicine RESEARCH Open Access Inflammatory breast cancer microenvironment repertoire based on DNA methylation data deconvolution reveals actionable targets to enhance the treatment efficacy Naiade Calanca 1,2†, Flavia Lima Costa Faldoni 1†, Cristiano Pádua Souza3, Jeferson Santos Souza4, Bianca Elen de Souza Alves5, Milena Botelho Pereira Soares4,6, Deysi VivianaTenazoa Wong5, Roberto César Pereira Lima-Junior5, Fabio Albuquerque Marchi7,8, Claudia Aparecida Rainho2 and Silvia Regina Rogatto 1,9,10* Abstract Background Although the clinical signs of inflammatory breast cancer (IBC) resemble acute inflammation, the role played by infiltrating immune and stromal cells in this aggressive disease is uncharted. The tumor microenvironment (TME) presents molecular alterations, such as epimutations, prior to morphological abnormalities. These changes affect the distribution and the intricate communication between the TME components related to cancer prognosis and therapy response. Herein, we explored the global DNA methylation profile of IBC and surrounding tissues to estimate the microenvironment cellular composition and identify epigenetically dysregulated markers. Methods We used the HiTIMED algorithm to deconvolve the bulk DNA methylation data of 24 IBC and six surrounding non-tumoral tissues (SNT) (GSE238092) and determine their cellular composition. The prognostic relevance of cell types infiltrating IBC and their relationship with clinicopathological variables were investigated. CD34 (endothelial cell marker) and CD68 (macrophage marker) immunofluorescence staining was evaluated in an independent set of 17 IBC and 16 non-IBC samples. Results We found lower infiltration of endothelial, stromal, memory B, dendritic, and natural killer cells in IBC than in SNT samples. Higher endothelial cell (EC) and stromal cell content were related to better overall survival. EC proportions positively correlated with memory B and memory CD8+ T infiltration in IBC. Immune and EC markers exhibited distinct DNA methylation profiles between IBC and SNT samples, revealing hypermethylated regions †Naiade Calanca, Flavia Lima Costa Faldoni contributed equally to this work. *Correspondence: Silvia Regina Rogatto [silvia. rogatto@unesp.br](silvia. rogatto@unesp.br); [silvia. regina. rogatto@rsyd.dk](silvia. regina. rogatto@rsyd.dk) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Calanca et al. Journal of Translational Medicine (2024) 22:735 Page 2 of 13 mapped to six genes (CD40, CD34, EMCN, HLA-G, PDPN, and TEK) . We identified significantly higher CD34 and CD68 protein expres

FAQs

What is the main goal of analyzing DNA methylation in inflammatory breast cancer?

To estimate the cellular composition of the tumor microenvironment and identify epigenetically dysregulated markers that relate to prognosis and treatment response.

Which method was used to deconvolve bulk DNA methylation data, and what samples were analyzed?

HiTIMED was used to deconvolve bulk DNA methylation data from 24 IBC and six surrounding non-tumoral tissues; cell infiltrates were then assessed for prognostic relevance and validated with immunofluorescence in an independent sample set.

What immune or stromal differences were found between IBC and surrounding non-tumoral tissues?

IBC showed lower infiltration of endothelial, stromal, memory B, dendritic, and natural killer cells, while higher endothelial and stromal content was associated with better overall survival.

Which findings suggest potential therapeutic targets or strategies?

Distinct DNA methylation profiles between IBC and non-IBC mapped to genes including CD40, CD34, EMCN, HLA-G, PDPN, and TEK, and dysregulated markers were proposed as actionable through combinations of immunotherapy and epigenetic drugs.

Sep 21, 2026

Uploaded by Oliver