Enhancing the biological relevance of secretome-based proteomics by linking tumor cell proliferation and protein secretion

Josep Gregori, Olga Méndez, Theodora Katsila, Mireia Pujals, Cándida Salvans, Laura Villarreal, Joaquin Arribas, Josep Tabernero, Alex Sánchez, Josep Villanueva

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Secretome profiling has become a methodology of choice for the identification of tumor biomarkers. We hypothesized that due to the dynamic nature of secretomes cellular perturbations could affect their composition but also change the global amount of protein secreted per cell. We confirmed our hypothesis by measuring the levels of secreted proteins taking into account the amount of proteome produced per cell. Then, we established a correlation between cell proliferation and protein secretion that explained the observed changes in global protein secretion. Next, we implemented a normalization correcting the statistical results of secretome studies by the global protein secretion of cells into a generalized linear model (GLM). The application of the normalization to two biological perturbations on tumor cells resulted in drastic changes in the list of statistically significant proteins. Furthermore, we found that known epithelial-to-mesenchymal transition (EMT) effectors were only statistically significant when the normalization was applied. Therefore, the normalization proposed here increases the sensitivity of statistical tests by increasing the number of true-positives. From an oncology perspective, the correlation between protein secretion and cellular proliferation suggests that slow-growing tumors could have high-protein secretion rates and consequently contribute strongly to tumor paracrine signaling. © 2014 American Chemical Society.
Original languageEnglish
Pages (from-to)3706-3721
JournalJournal of Proteome Research
Volume13
Issue number8
DOIs
Publication statusPublished - 1 Aug 2014

Keywords

  • Biomarker Discovery
  • epidermal growth factor receptor (EGFR)
  • epithelial to mesenchymal transition (EMT)
  • generalized linear model (GLM)
  • secretome
  • spectral count

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