Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism

Research output: Contribution to journalArticle

Abstract

In this study, we have analyzed human primary lung adenocarcinoma tumors using global mass spectrometry to elucidate the biological mechanisms behind relapse post surgery. In total, we identified over 3000 proteins with high confidence. Supervised multivariate analysis was used to select 132 proteins separating the prognostic groups. Based on in-depth bioinformatics analysis, we hypothesized that the tumors with poor prognosis had a higher glycolytic activity and HIF activation. By measuring the bioenergetic cellular index of the tumors, we could detect a higher dependency of glycolysis among the tumors with poor prognosis. Further, we could also detect an up-regulation of HIF1 alpha mRNA expression in tumors with early relapse. Finally, we selected three proteins that were upregulated in the poor prognosis group (cathepsin D, ENO1, and VDAC1) to confirm that the proteins indeed originated from the tumor and not from a stromal or inflammatory component. Overall, these findings show how in-depth analysis of clinical material can lead to an increased understanding of the molecular mechanisms behind tumor progression.

Details

Authors
  • Maria Pernemalm
  • Luigi De Petris
  • Rui M. Branca
  • Jenny Forshed
  • Lena Kanter
  • Jean-Charles Soria
  • Philippe Girard
  • Pierre Validire
  • Yudi Pawitan
  • Joost van den Oord
  • Vladimir Lazar
  • Sven Påhlman
  • Rolf Lewensohn
  • Janne Lehtio
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • NSCLC, adenocarcinoma, relapse, glycolysis, hypoxia, HIF1, ENO1, VDAC1, CTSD, Warburg, prognosis, peptide isoelectric focusing
Original languageEnglish
Pages (from-to)3934-3943
JournalJournal of Proteome Research
Volume12
Issue number9
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes