Comparative profiling of whole-cell and exosome samples reveals protein signatures that stratify breast cancer subtypes

Sep 21, 2026

Uploaded by Oliver

Identifying novel breast cancer biomarkers improves patient stratification, enhances therapeutic outcomes, and enables non-invasive diagnostics. The study compares proteomic profiles of whole-cell and exosomal samples across representative breast cancer cell subtypes to assess extracellular vesicles as liquid-biopsy biomarkers. Differentially expressed proteins in both whole-cell and exosome samples discriminate subtypes, with exosome profiles reflecting the originating breast cancer cells. Results support exosome-based disease biomarkers and include an open interactive web tool for exploring protein-signature data in classification.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

Introduction

Graphical Abstract

Cellular and Molecular Life Sciences (2024) 81:363 [https://doi.org/10.1007/s00018-024-05403-z](https://doi.org/10.1007/s00018-024-05403-z) Cellular and Molecular Life Sciences ORIGINAL ARTICLE Comparative profiling of whole-cell and exosome samples reveals protein signatures that stratify breast cancer subtypes Zoraida Andreu1,2,3,4 · Marta R. Hidalgo2,3,5 · Esther Masiá1,2,6 · Sergio Romera-Giner3 · Pablo Malmierca-Merlo3 · José A. López-Guerrero2,4,7 · Francisco García-García2,3 · María J. Vicent1,2,6 Received: 26 May 2024 / Revised: 2 August 2024 / Accepted: 7 August 2024 © The Author(s) 2024 Abstract Identifying novel breast cancer biomarkers will improve patient stratification, enhance therapeutic outcomes, and help develop non-invasive diagnostics. We compared the proteomic profiles of whole-cell and exosomal samples of representative breast cancer cell subtypes to evaluate the potential of extracellular vesicles as non-invasive disease biomarkers in liquid biopsies. Overall, differentially-expressed proteins in whole-cell and exosome samples (which included markers for invasion, metastasis, angiogenesis, and drug resistance) effectively discriminated subtypes; furthermore, our results confirmed that the proteomic profile of exosomes reflects breast cancer cell-of-origin, which underscores their potential as disease biomarkers. Our study will contribute to identifying biomarkers that support breast cancer patient stratification and developing novel therapeutic strategies. We include an open, interactive web tool to explore the data as a molecular resource that can explain the role of these protein signatures in breast cancer classification. Zoraida Andreu and Marta R. Hidalgo contributed equally to this work. 􀀍 Zoraida Andreu [zandreu@fivo.org](zandreu@fivo.org) 􀀍 Francisco García-García[fgarcia@cipf.es](fgarcia@cipf.es) 􀀍 María J. Vicent [mjvicent@cipf.es](mjvicent@cipf.es) 1 Polymer Therapeutics Laboratory and Screening Platform, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain 2 IVO-CIPF Joint Cancer Research Unit, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain 3 Computational Biomedicine Laboratory, Príncipe Felipe Research Center (CIPF), Av. Eduardo Primo Yúfera 3, Valencia 46012, Spain 4 Laboratory of Molecular Biology, Foundation of the Valencian Institute of Oncology, Valencia 46009, Spain 5 Department of Mathematics, School of Mathematics, University of Valencia, Valencia 46010, Spain 6 CIBERONC, Carlos III Health Institute (IISCIII), Madrid, Spain 7 Department of Pathology, Medical School, Catholic University of Valencia ‘San Vicente Mártir’, Valencia 46001, Spain 1 3 Graphical Abstract (A) We quantified proteomic profiles of breast cancer cells (BCCs) and breast cancer-derived exosomes (BCDEs) samples from four breast cancer cell lines representative of common breast cancer subtypes – Her2-positive (Her2, MDA-MB-453), LuminalA (LA, MCF7), Luminal B (LB, ZR-75), and triple-negative (TN, MDA-MB-231) . (B) We independently performed four comparisons for BCCs and BCDEs, comparing each cell line against the remaining three. (C) We identified differentially-expressed proteins (DEPs) for BCCs and BCDEs, defined protein signatures, and functionally analyzed resulting networks. Through pathway inference analysis (PIA), we identified Kyoto Encyclopedia of genes and genomes (KEGG) subpaths and biological Gene Ontology (GO) terms that displayed differential activation. (D) We validated our proteomic signature using the Cancer Genome Atlas (TCGA) and the Cancer ProteomeAtlas (TCPA) databases, verified that differentially-activated pathways in BCDEs caused a corresponding response in receptor cells, and confirmed that the BCDE proteomic signature reflects their cell-of-origin and identifies candidate disease biomarkers in liquid biopsies Introduction Despite ongoing advances, breast cancer rem

FAQs

How does the study compare whole-cell and exosome samples?

It compares proteomic profiles of whole-cell and exosomal samples from representative breast cancer cell subtypes to evaluate extracellular vesicles as non-invasive biomarkers in liquid biopsies.

What do the results show about protein signatures across subtypes?

Differentially expressed proteins effectively discriminate breast cancer subtypes, including proteins associated with invasion, metastasis, angiogenesis, and drug resistance.

Why are exosome profiles important for breast cancer biomarker development?

The proteomic profile of exosomes reflects the breast cancer cell of origin, supporting their potential as disease biomarkers for classification and patient stratification.

Sep 21, 2026

Uploaded by Oliver