title: Glycoproteomic analysis of prostate cancer tissues by SWATH mass spectrometry discovers N-acylethanolamine acid amidase and protein tyrosine kinase 7 as signatures for tumor aggressiveness.
abstract: The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa.
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: ¶Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21231;
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;
authors.forename: Atul
authors.initials: A
authors.lastname: Sethi
authors.affiliation: ¶Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21231;
authors.forename: Qing K
authors.initials: QK
authors.lastname: Li
authors.affiliation: ¶Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21231;
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;
authors.forename: Ben
authors.initials: B
authors.lastname: Collins
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;
authors.forename: Ludovic C J
authors.initials: LC
authors.lastname: Gillet
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland;
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollscheid
authors.affiliation: ¶Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21231; hzhang32@jhmi.edu aebersold@imsb.biol.ethz.ch.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the ‡Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland; **Faculty of Science, University of Zurich, 8057 Zurich, Switzerland hzhang32@jhmi.edu aebersold@imsb.biol.ethz.ch.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000581:Amidohydrolases; C523108:NAAA protein, human
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