Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches

2010 ◽  
Author(s):  
Natasha Kyprianou
Keyword(s):  
Prostate Cancer ◽  
Biomarker Discovery ◽  
Mechanistic Studies

scholarly journals Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 5-36 ◽  
Author(s):  
Katarina Davalieva ◽  
Momir Polenakovic
Keyword(s):  
Prostate Cancer ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
Molecular Level ◽  
Specific Antigen ◽  
Shotgun Proteomics ◽  
Comparative Proteomics ◽  
Label Free ◽  
The Past ◽  
Proteomics Research

Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.

scholarly journals Accelerated Protein Biomarker Discovery from FFPE tissue samples using Single-shot, Short Gradient Microflow SWATH MS

2019 ◽  
Author(s):  
Rui Sun ◽  
Christie Hunter ◽  
Chen Chen ◽  
Weigang Ge ◽  
Nick Morrice ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biomarker Discovery ◽  
Single Shot ◽  
Protein Biomarkers ◽  
Differential Abundance ◽  
Tissue Samples ◽  
Peptide Precursors ◽  
High Consistency ◽  
Method R ◽  
Acquisition Method

ABSTRACTWe report and evaluated a microflow, single-shot, short gradient SWATH MS method intended to accelerate the discovery and verification of protein biomarkers in clinical specimens. The method uses 15-min gradient microflow-LC peptide separation, an optimized SWATH MS window configuration and OpenSWATH software for data analysis.We applied the method to a cohort 204 of FFPE prostate tissue samples from 58 prostate cancer patients and 10 prostatic hyperplasia patients. Altogether we identified 27,976 proteotypic peptides and 4,043 SwissProt proteins from these 204 samples. Compared to a reference SWATH method with 2-hour gradient the accelerated method consumed only 27% instrument time, quantified 80% proteins and showed reduced batch effects. 3,800 proteins were quantified by both methods in two different instruments with relatively high consistency (r = 0.77). 75 proteins detected by the accelerated method with differential abundance between clinical groups were selected for further validation. A shortlist of 134 selected peptide precursors from the 75 proteins were analyzed using MRM-HR, exhibiting high quantitative consistency with the 15-min SWATH method (r = 0.89) in the same sample set. We further verified the capacity of these 75 proteins in separating benign and malignant tissues (AUC = 0.99) in an independent prostate cancer cohort (n=154).Overall our data show that the single-shot short gradient microflow-LC SWATH MS method achieved about 4-fold acceleration of data acquisition with reduced batch effect and a moderate level of protein attrition compared to a standard SWATH acquisition method. Finally, the results showed comparable ability to separate clinical groups.

scholarly journals Prostate cancer serum biomarker discovery through proteomic analysis of alpha-2 macroglobulin protein complexes

2008 ◽  
Vol 2 (9) ◽  
pp. 1223-1233 ◽  
Author(s):  
Earle F. Burgess ◽  
Amy-Joan L. Ham ◽  
David L. Tabb ◽  
Dean Billheimer ◽  
Bruce J. Roth ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proteomic Analysis ◽  
Biomarker Discovery ◽  
Protein Complexes ◽  
Serum Biomarker

scholarly journals Integrated Analyses of Proteins and Their Glycans in a Magnetic Bead–Based Multiplex Assay Format

2013 ◽  
Vol 59 (1) ◽  
pp. 315-324 ◽  
Author(s):  
Danni Li ◽  
Hanching Chiu ◽  
Jing Chen ◽  
Hui Zhang ◽  
Daniel W Chan
Keyword(s):  
Prostate Cancer ◽  
Magnetic Beads ◽  
Biomarker Discovery ◽  
Magnetic Bead ◽  
Protein Quantification ◽  
Integrated System ◽  
Clinical Samples ◽  
Improved Performance ◽  
Integrated Detection ◽  
Cancer Tissues

BACKGROUND Well-annotated clinical samples are valuable resources for biomarker discovery and validation. Multiplex and integrated methods that simultaneously measure multiple analytes and generate integrated information about these analytes from a single measurement are desirable because these methods help conserve precious samples. We developed a magnetic bead–based system for multiplex and integrated glycoprotein quantification by immunoassays and glycan detection by lectin immunosorbent assays (LISAs). METHODS Magnetic beads coupled with antibodies were used for capturing proteins of interest. Biotinylated antibodies in combination with streptavidin-labeled phycoerythrin were used for protein quantification. In the LISAs, biotinylated detection antibodies were replaced by biotinylated lectins for glycan detection. RESULTS Using tissue inhibitor of metallopeptidase 1 (TIMP-1), tissue plasminogen activator, membrane metallo-endopeptidase, and dipeptidyl peptidase-IV (DPP-4) as models, we found that the multiplex integrated system was comparable to single immunoassays in protein quantification and LISAs in glycan detection. The merits of this system were demonstrated when applied to well-annotated prostate cancer tissues for validation of biomarkers in aggressive prostate cancer. Because of the system's multiplex ability, we used only 300 ng of tissue protein for the integrated detection of glycans in these proteins. Fucosylated TIMP-1 and DPP-4 offered improved performance over the proteins in distinguishing aggressive and nonaggressive prostate cancer. CONCLUSIONS The multiplex and integrated system conserves samples and is a useful tool for validation of glycoproteins and their glycoforms as biomarkers.

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