Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis

Marco Pedrazzi, Silvia Vercellone, Elettra Barberis, Michela Capraro, Roberta De Tullio, Federico Cresta, Rosaria Casciaro, Carlo Castellani, Mauro Patrone, Emilio Marengo, Paola Lecca, Paola Melotti, Claudio Sorio, Marcello Manfredi, Monica Averna

Research output: Contribution to journalArticlepeer-review


The aim of this study was the identification of specific proteomic profiles, related to a restored cystic fibrosis transmembrane conductance regulator (CFTR) activity in cystic fibrosis (CF) leukocytes before and after ex vivo treatment with the potentiator VX770. We used leukocytes, isolated from CF patients carrying residual function mutations and eligible for Ivacaftor therapy, and performed CFTR activity together with proteomic analyses through micro-LC-MS. Bioinformatic analyses of the results obtained revealed the downregulation of proteins belonging to the leukocyte transendothelial migration and regulation of actin cytoskeleton pathways when CFTR activity was rescued by VX770 treatment. In particular, we focused our attention on matrix metalloproteinase 9 (MMP9), because the high expression of this protease potentially contributes to parenchyma lung destruction and dysfunction in CF. Thus, the downregulation of MMP9 could represent one of the possible positive effects of VX770 in decreasing the disease progression, and a potential biomarker for the prediction of the efficacy of therapies targeting the defect of Cl- transport in CF.

Original languageEnglish
JournalInternational journal of molecular sciences
Issue number8
Publication statusPublished - Apr 10 2021


  • Actin Cytoskeleton/genetics
  • Adult
  • Aminophenols/pharmacology
  • Biomarkers/blood
  • Cell Movement/drug effects
  • Cystic Fibrosis/blood
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Female
  • Gene Expression Regulation/drug effects
  • Humans
  • Leukocytes, Mononuclear/drug effects
  • Male
  • Matrix Metalloproteinase 9/genetics
  • Proteome/genetics
  • Quinolones/pharmacology


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