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Phosphoproteins in extracellular vesicles as candidate markers for breast cancer.


ABSTRACT: The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.

SUBMITTER: Chen IH 

PROVIDER: S-EPMC5373352 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Phosphoproteins in extracellular vesicles as candidate markers for breast cancer.

Chen I-Hsuan IH   Xue Liang L   Hsu Chuan-Chih CC   Paez Juan Sebastian Paez JS   Pan Li L   Andaluz Hillary H   Wendt Michael K MK   Iliuk Anton B AB   Zhu Jian-Kang JK   Tao W Andy WA  

Proceedings of the National Academy of Sciences of the United States of America 20170307 12


The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. U  ...[more]

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