Proteomics

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Phosphoproteins in extracellular vehicles 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 from biofluids for disease diagnosis remains elusive. Here we demonstrate, for the first time, a strategy to isolate and identify phosphoproteins in extracellular vehicles from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides, representing 2108 phosphoproteins, in EVs isolated from small volume of plasma samples. Using label-free quantitative proteomics, we quantified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer than in healthy controls. Multiple novel biomarkers were validated in 13 patients using Paralleled Reaction Monitoring and antibody- and non-antibody based assays. The study demonstrated that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: I-Hsuan Chen  

LAB HEAD: Weiguo Andy Tao

PROVIDER: PXD005214 | Pride | 2017-03-23

REPOSITORIES: Pride

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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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