期刊
PROTEOMICS CLINICAL APPLICATIONS
卷 7, 期 9-10, 页码 677-689出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.201200134
关键词
Expressed prostatic secretion; Glycomics; N-linked glycosylation; Prostate cancer; Urine exosome
资金
- National Institutes of Health/National Cancer Institute [R21CA137704, R01CA135087]
- state of South Carolina Smart-State Endowed Research program
- National Cancer Institute (NCI) [R01 CA120206, U01 CA168856]
- Hepatitis B Foundation
- [P30 CA138313]
PurposeUsing prostatic fluids rich in glycoproteins like prostate-specific antigen and prostatic acid phosphatase (PAP), the goal of this study was to identify the structural types and relative abundance of glycans associated with prostate cancer status for subsequent use in emerging MS-based glycopeptide analysis platforms. Experimental designA series of pooled samples of expressed prostatic secretions (EPS) and exosomes reflecting different stages of prostate cancer disease were used for N-linked glycan profiling by three complementary methods, MALDI-TOF profiling, normal-phase HPLC separation, and triple quadropole MS analysis of PAP glycopeptides. ResultsGlycan profiling of N-linked glycans from different EPS fluids indicated a global decrease in larger branched tri- and tetra-antennary glycans. Differential exoglycosidase treatments indicated a substantial increase in bisecting N-acetylglucosamines correlated with disease severity. A triple quadrupole MS analysis of the N-linked glycopeptides sites from PAP in aggressive prostate cancer pools was done to cross-reference with the glycan profiling data. Conclusion and clinical relevanceChanges in glycosylation as detected in EPS fluids reflect the clinical status of prostate cancer. Defining these molecular signatures at the glycopeptide level in individual samples could improve current approaches of diagnosis and prognosis.
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