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.

Cited by papers we hold 9

• Glycosylation Changes in Prostate Cancer Progression · 2021
  Not checked
• A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry–Based Glycoproteomics · 2021
  No notice
• Integrating SWATH-MS Proteomics and Transcriptome Analysis Identifies CHI3L1 as a Plasma Biomarker for Early Gastric Cancer · 2020
  Not checked
• Reproducibility, Specificity and Accuracy of Relative Quantification Using Spectral Library-based Data-independent Acquisition · 2020
  No notice
• The crucial role of multiomic approach in cancer research and clinically relevant outcomes · 2018
  No notice
• Data‐independent acquisition‐based SWATH‐MS for quantitative proteomics: a tutorial · 2018
  No notice
• Advances in mass spectrometry-based clinical biomarker discovery · 2016
  No notice
• Applications of targeted proteomics in systems biology and translational medicine · 2015
  No notice
• Quantitative variability of 342 plasma proteins in a human twin population · 2015
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.