Proteomics

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Targeted Mass Spectrometry of a Clinically Relevant PSA Variant from Post-DRE Urines for Quantitation and Genotype Determination


ABSTRACT: The rs17632542 SNP results in lower serum PSA levels which may further mitigate against its clinical utility as a prostate cancer biomarker. Post-DRE urine is a minimally invasive fluid that is currently utilized in prostate cancer diagnosis. We have used targeted MS to detect and quantitate the variant protein in urine. Experimental Design Fifty-three urines collected after digital rectal exam (post-DRE urine) from rs17632542 genotyped individuals were processed and analyzed by LC-MS in a double-blinded randomized study. The ability to distinguish between homozygous wild-type, heterozygous, or homozygous variant was examined prior to unblinding. Results Stable-isotope labeled peptides were used in the detection and quantitation of peptides of interest in each sample. Three peptides were monitored by LC-MS using a PRM method. Analysis of the raw data using Skyline allowed for peak detection and area extraction. Using these data, groupings were predicted using hierarchical clustering in R. Accuracy of the predictions showed 100% concordance across the 53 samples, including individuals homozygous and heterozygous for the SNP. Conclusions and clinical relevance The study demonstrates that MS based peptide variant quantitation in urine could be useful in determining patient genotype with high accuracy to complement currently used PSA screening.

ORGANISM(S): Homo Sapiens

SUBMITTER: Joe Otto  

PROVIDER: PXD017257 | panorama | Mon Sep 14 00:00:00 BST 2020

REPOSITORIES: PanoramaPublic

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Targeted Mass Spectrometry of a Clinically Relevant PSA Variant from Post-DRE Urines for Quantitation and Genotype Determination.

Otto Joseph J JJ   Correll Vanessa L VL   Engstroem Hampus A HA   Hitefield Naomi L NL   Main Brian P BP   Albracht Brenna B   Johnson-Pais Teresa T   Yang Li Fang LF   Liss Michael M   Boutros Paul C PC   Kislinger Thomas T   Leach Robin J RJ   Semmes Oliver J OJ   Nyalwidhe Julius O JO  

Proteomics. Clinical applications 20200709 6


<h4>Purpose</h4>The rs17632542 single nucleotide polymorphism (SNP) results in lower serum prostate specific antigen (PSA) levels which may further mitigate against its clinical utility as a prostate cancer biomarker. Post-digital rectal exam (post-DRE) urine is a minimally invasive fluid that is currently utilized in prostate cancer diagnosis. To detect and quantitate the variant protein in urine.<h4>Experimental design</h4>Fifty-three post-DRE urines from rs17632542 genotyped individuals proce  ...[more]

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