Profiling protein post-translational modifications in plasma-derived extracellular vesicles as fingerprints for breast cancer subtypes.
14 affiliations
- 1Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
- 2Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
- 3Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA.
- 4School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, 47907, USA.
- 5Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
- 6Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Gujarat, India, 390002.
- 7Department of Biochemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA.
- 8Tymora Analytical Operations, West Lafayette, IN, 47906, USA.
- 9Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
- 10Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
- 11Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
- 12Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
- 13Tymora Analytical Operations, West Lafayette, IN, 47906, USA. [email protected].
- 14Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA. [email protected].
Abstract
Background
Addressing tumor heterogeneity in breast cancer research is crucial, given the distinct subtypes like triple-negative, luminal A/B, and HER2, requiring precise differentiation for effective treatment. This study introduces a non-invasive method by analyzing post-translationally modified proteins in plasma extracellular vesicles, which play a role in immune regulation and intercellular communication. Examining modifications like phosphorylation, acetylation and glycosylation in extracellular vesicles provides insights into breast cancer dynamics. One hundred and one plasma samples from luminal A/B breast cancer, triple-negative breast cancer and healthy individuals underwent discovery and validation experiments.Result
The study identified over 28,000 unique non-modified peptides, 5,000 phosphopeptides, 680 acetyl peptides and 1,300 glycopeptides that are successfully characterized. Bioinformatics analyses revealed significant overexpression of 815 non-modified proteins, 3,958 phosphopeptides, 352 acetyl peptides and 895 glycopeptides in luminal A/B breast cancer or triple-negative breast cancer subtypes. Phosphorylated and glycosylated PD-L1 peptides emerge as potential markers for breast cancer, regardless of subtype. Aligning the findings with literature and PAM50 gene signatures highlights markers correlated with lower survival rates. The study also reports 123 scheduled parallel reaction monitoring analyses, leveraging machine learning to pinpoint a panel of specific modification sites with high accuracy for subtype differentiation.Conclusions
This research reveals diagnostic markers and enhances understanding of the molecular landscape, contributing to more effective and personalized breast cancer diagnostics and treatments.
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BibTeX
@article{hadisurya2026profiling,
title = {{Profiling protein post-translational modifications in plasma-derived extracellular vesicles as fingerprints for breast cancer subtypes.}},
author = {Marco Hadisurya and Hillary Andaluz Aguilar and I-Hsuan Chen and Mengting Xu and Juan Sebastian Paez and Rachit Bisht and Jyoti Singh and Zheng-Chi Lee and Amirhesam Mashaollahi and Anton Iliuk and Weizhou Zhang and W Andy Tao},
journal = {Genome biology},
year = {2026},
month = jul,
doi = {10.1186/s13059-026-04212-w},
url = {https://europepmc.org/article/MED/42902395},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Profiling protein post-translational modifications in plasma-derived extracellular vesicles as fingerprints for breast cancer subtypes.
AU - Marco Hadisurya
AU - Hillary Andaluz Aguilar
AU - I-Hsuan Chen
AU - Mengting Xu
AU - Juan Sebastian Paez
AU - Rachit Bisht
AU - Jyoti Singh
AU - Zheng-Chi Lee
AU - Amirhesam Mashaollahi
AU - Anton Iliuk
AU - Weizhou Zhang
AU - W Andy Tao
PY - 2026
DA - 2026/07/01
JO - Genome biology
DO - 10.1186/s13059-026-04212-w
UR - https://europepmc.org/article/MED/42902395
AB - Background Addressing tumor heterogeneity in breast cancer research is crucial, given the distinct subtypes like triple-negative, luminal A/B, and HER2, requiring precise differentiation for effective treatment. This study introduces a non-invasive method by analyzing post-translationally modified proteins in plasma extracellular vesicles, which play a role in immune regulation and intercellular communication. Examining modifications like phosphorylation, acetylation and glycosylation in extracellular vesicles provides insights into breast cancer dynamics. One hundred and one plasma samples from luminal A/B breast cancer, triple-negative breast cancer and healthy individuals underwent discovery and validation experiments.Result The study identified over 28,000 unique non-modified peptides, 5,000 phosphopeptides, 680 acetyl peptides and 1,300 glycopeptides that are successfully characterized. Bioinformatics analyses revealed significant overexpression of 815 non-modified proteins, 3,958 phosphopeptides, 352 acetyl peptides and 895 glycopeptides in luminal A/B breast cancer or triple-negative breast cancer subtypes. Phosphorylated and glycosylated PD-L1 peptides emerge as potential markers for breast cancer, regardless of subtype. Aligning the findings with literature and PAM50 gene signatures highlights markers correlated with lower survival rates. The study also reports 123 scheduled parallel reaction monitoring analyses, leveraging machine learning to pinpoint a panel of specific modification sites with high accuracy for subtype differentiation.Conclusions This research reveals diagnostic markers and enhances understanding of the molecular landscape, contributing to more effective and personalized breast cancer diagnostics and treatments.
SN - 1474-7596
SN - 1474-760X
ER -