Phosphoproteins in extracellular vesicles as candidate markers for breast cancer

被引:427
作者
Chen, I-Hsuan [1 ]
Xue, Liang [1 ]
Hsu, Chuan-Chih [1 ]
Paez, Juan Sebastian Paez [1 ]
Pan, Li [2 ]
Andaluz, Hillary [3 ]
Wendt, Michael K. [2 ]
Iliuk, Anton B. [4 ]
Zhu, Jian-Kang [1 ,5 ,6 ,7 ]
Tao, W. Andy [1 ,2 ,3 ,8 ]
机构
[1] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
[3] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[4] Tymora Analyt Operat, Dept Innovat, W Lafayette, IN 47906 USA
[5] Purdue Univ, Dept Hort & Landscape Architecture, W Lafayette, IN 47907 USA
[6] Chinese Acad Sci, Shanghai Ctr Plant Stress Biol, Shanghai 201602, Peoples R China
[7] Chinese Acad Sci, Ctr Excellence Mol Plant Sci, Shanghai 201602, Peoples R China
[8] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA
基金
美国国家科学基金会;
关键词
phosphoproteins; proteomics; extracellular vesicles; mass spectrometry; biomarker; ION AFFINITY-CHROMATOGRAPHY; INTERACTION NETWORKS; SIGNALING NETWORKS; PANCREATIC-CANCER; MASS-SPECTROMETRY; EXOSOMES; PROTEOMICS; CELLS; ENRICHMENT; BLOOD;
D O I
10.1073/pnas.1618088114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:3175 / 3180
页数:6
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