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

Nat Commun. 2019 Jun 7;10(1):2524. doi: 10.1038/s41467-019-10513-5.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Prostate / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Proteins / metabolism*
  • Proteolysis*
  • RNA Stability*
  • RNA, Messenger / metabolism*
  • Sequence Analysis, RNA

Substances

  • Proteins
  • RNA, Messenger