Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry

Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood prostate‐specific antigen test has facilitated early detection and intervention of prostate cancer. However, blood prostate‐specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. In the current study, we evaluated urine specimens from prostate cancer patients using LC‐MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N‐linked glycosite‐containing peptides and LC‐MS/MS. A total of 2923 unique glycosite‐containing peptides were identified. Glycoproteomic comparison on urine and tissues from aggressive and non‐aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer.

[1]  J. Presti.  Prostate biopsy strategies , 2007, Nature Clinical Practice Urology.

[2]  Hui Zhang,et al.  Overexpression of α (1,6) fucosyltransferase associated with aggressive prostate cancer. , 2014, Glycobiology.

[3]  A. Taille,et al.  Urine biomarkers in prostate cancer , 2010, Nature Reviews Urology.

[4]  S. Dhanasekaran,et al.  Methylacyl Coenzyme A Racemase as a Tissue Biomarker for Prostate Cancer , 2017 .

[5]  D. Chan,et al.  Analysis of N-glycoproteins using genomic N-glycosite prediction. , 2013, Journal of proteome research.

[6]  Yuan Tian,et al.  Identification, prioritization, and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody‐based assays on tissue specimens , 2013, Proteomics.

[7]  Paul Aiyetan,et al.  Comprehensive analysis of protein glycosylation by solid-phase extraction of N-linked glycans and glycosite-containing peptides , 2016, Nature Biotechnology.

[8]  R L Vessella,et al.  Prostatic specific antigen and prostatic acid phosphatase in the monitoring and staging of patients with prostatic cancer. , 1987, The Journal of urology.

[9]  X. Breakefield,et al.  Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer , 2009, British Journal of Cancer.

[10]  P. Schellhammer,et al.  Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. , 2002, Cancer research.

[11]  M. Kosanović,et al.  Isolation of urinary extracellular vesicles from Tamm- Horsfall protein-depleted urine and their application in the development of a lectin-exosome-binding assay. , 2014, BioTechniques.

[12]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[13]  Moemen AK Abdalla,et al.  Potential Urinary miRNA Biomarker Candidates for the Accurate Detection of Prostate Cancer among Benign Prostatic Hyperplasia Patients , 2014, Journal of Cancer.

[14]  A. Jemal,et al.  Cancer statistics, 2015 , 2015, CA: a cancer journal for clinicians.

[15]  C. Bertozzi,et al.  Glycans in cancer and inflammation — potential for therapeutics and diagnostics , 2005, Nature Reviews Drug Discovery.

[16]  Hui Zhang,et al.  Cancer Biomarker Discovery in Plasma Using a Tissue-targeted Proteomic Approach , 2007, Cancer Epidemiology Biomarkers & Prevention.

[17]  D. Chan,et al.  Aberrant glycosylation associated with enzymes as cancer biomarkers , 2011, Clinical Proteomics.

[18]  José A García,et al.  Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer , 2005, BMC Cancer.

[19]  J. X. Pang,et al.  Biomarker discovery in urine by proteomics. , 2002, Journal of proteome research.

[20]  Ruedi Aebersold,et al.  Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry , 2003, Nature Biotechnology.

[21]  Sudhir Srivastava,et al.  Biomarkers for prostate cancer detection. , 2007, The Journal of urology.

[22]  Mehdi Mirzaei,et al.  Less label, more free: Approaches in label‐free quantitative mass spectrometry , 2011, Proteomics.

[23]  C. Stephan,et al.  The usefulness of serum human kallikrein 11 for discriminating between prostate cancer and benign prostatic hyperplasia. , 2003, Cancer research.

[24]  J. Falcón-Pérez,et al.  Microarray‐Based Identification of Lectins for the Purification of Human Urinary Extracellular Vesicles Directly from Urine Samples , 2014, Chembiochem : a European journal of chemical biology.

[25]  E. Petricoin,et al.  Serum proteomic patterns for detection of prostate cancer. , 2002, Journal of the National Cancer Institute.

[26]  Terukazu Nakamura,et al.  Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. , 2002, Cancer research.

[27]  C. Ward,et al.  Surface Glycosylation Profiles of Urine Extracellular Vesicles , 2013, PloS one.

[28]  Jing Chen,et al.  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 , 2014, Molecular & Cellular Proteomics.

[29]  S. Loening,et al.  Matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinase‐1 and the complex of metalloproteinase‐1/tissue inhibitor in plasma of patients with prostate cancer , 1997, International journal of cancer.

[30]  Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy. , 2006, Journal of the National Cancer Institute.

[31]  Roman Kaliszan,et al.  Urine metabolic fingerprinting using LC-MS and GC-MS reveals metabolite changes in prostate cancer: A pilot study. , 2015, Journal of pharmaceutical and biomedical analysis.

[32]  Hui Zhang,et al.  Integrated Proteomic and Glycoproteomic Analyses of Prostate Cancer Cells Reveal Glycoprotein Alteration in Protein Abundance and Glycosylation* , 2015, Molecular & Cellular Proteomics.

[33]  Yuan Tian,et al.  Quantitative proteomic analysis of ovarian cancer cells identified mitochondrial proteins associated with paclitaxel resistance , 2009, Proteomics. Clinical applications.

[34]  H. Woo,et al.  Current Status of Biomarkers for Prostate Cancer , 2013, International journal of molecular sciences.

[35]  S. Kung,et al.  GOASVM: a subcellular location predictor by incorporating term-frequency gene ontology into the general form of Chou's pseudo-amino acid composition. , 2013, Journal of theoretical biology.

[36]  Yuan Tian,et al.  Identification of glycoproteins associated with different histological subtypes of ovarian tumors using quantitative glycoproteomics , 2011, Proteomics.

[37]  D. Chan,et al.  [-2]proenzyme prostate specific antigen for prostate cancer detection: a national cancer institute early detection research network validation study. , 2007, The Journal of urology.

[38]  A. Kuno,et al.  A strategy for discovery of cancer glyco‐biomarkers in serum using newly developed technologies for glycoproteomics , 2010, The FEBS journal.

[39]  M. Sánchez-Niño,et al.  Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine , 2013, PloS one.

[40]  Yuan Tian,et al.  Quantitative glycoproteomic analysis of optimal cutting temperature-embedded frozen tissues identifying glycoproteins associated with aggressive prostate cancer. , 2011, Analytical chemistry.

[41]  S. Hakomori,et al.  Glycosylation defining cancer malignancy: New wine in an old bottle , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Relationship between primary Gleason pattern on needle biopsy and clinicopathologic outcomes among men with Gleason score 7 adenocarcinoma of the prostate. , 2006, Urology.

[43]  J. Oesterling,et al.  Prostate-specific antigen as a marker for prostatic cancer: a monoclonal and a polyclonal immunoassay compared. , 1987, Clinical chemistry.

[44]  Hui Zhang,et al.  Inhibition of protein carbamylation in urea solution using ammonium-containing buffers. , 2014, Analytical biochemistry.

[45]  Hui Zhang,et al.  Solid phase extraction of N-linked glycopeptides using hydrazide tip. , 2013, Analytical chemistry.

[46]  Doug W. Mahoney,et al.  Subfractionation, characterization and in-depth proteomic analysis of glomerular membrane vesicles in human urine , 2013, Kidney international.

[47]  S. Batra,et al.  Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate epithelia, functions as a prostate-specific tumor suppressor. , 2014, Biochimica et biophysica acta.

[48]  Debashis Ghosh,et al.  alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. , 2002, JAMA.