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Comparative analysis of mRNA and protein degradation in prostate tissues indicates high stability of proteins


Abstract

Deterioration of biomolecules in clinical tissues is an inevitable pre-analytical process, which affects molecular measurements and thus potentially confounds conclusions from cohort analyses. Here, we investigate the degradation of mRNA and protein in 68 pairs of adjacent prostate tissue samples using RNA-Seq and SWATH mass spectrometry, respectively. To objectively quantify the extent of protein degradation, we develop a numerical score, the Proteome Integrity Number (PIN), that faithfully measures the degree of protein degradation. Our results indicate that protein degradation only affects 5.9% of the samples tested and shows negligible correlation with mRNA degradation in the adjacent samples. These findings are confirmed by independent analyses on additional clinical sample cohorts and across different mass spectrometric methods. Overall, the data show that the majority of samples tested are not compromised by protein degradation, and establish the PIN score as a generic and accurate indicator of sample quality for proteomic analyses.

Abstract

Deterioration of biomolecules in clinical tissues is an inevitable pre-analytical process, which affects molecular measurements and thus potentially confounds conclusions from cohort analyses. Here, we investigate the degradation of mRNA and protein in 68 pairs of adjacent prostate tissue samples using RNA-Seq and SWATH mass spectrometry, respectively. To objectively quantify the extent of protein degradation, we develop a numerical score, the Proteome Integrity Number (PIN), that faithfully measures the degree of protein degradation. Our results indicate that protein degradation only affects 5.9% of the samples tested and shows negligible correlation with mRNA degradation in the adjacent samples. These findings are confirmed by independent analyses on additional clinical sample cohorts and across different mass spectrometric methods. Overall, the data show that the majority of samples tested are not compromised by protein degradation, and establish the PIN score as a generic and accurate indicator of sample quality for proteomic analyses.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:7 June 2019
Deposited On:25 Jul 2019 12:10
Last Modified:25 Sep 2019 00:38
Publisher:Nature Publishing Group
ISSN:2041-1723
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-019-10513-5
PubMed ID:31175306

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