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

Pernemalm, Maria; De Petris, Luigi; Branca, Rui M.; Forshed, Jenny; Kanter, Lena; Soria, Jean-Charles; Girard, Philippe; Validire, Pierre; Pawitan, Yudi and van den Oord, Joost, et al. (2013) In Journal of Proteome Research 12(9). p.3934-3943
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,... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
keywords
NSCLC, adenocarcinoma, relapse, glycolysis, hypoxia, HIF1, ENO1, VDAC1, CTSD, Warburg, prognosis, peptide isoelectric focusing
in
Journal of Proteome Research
volume
12
issue
9
pages
3934 - 3943
publisher
The American Chemical Society
external identifiers
  • wos:000330147800011
  • scopus:84883766689
ISSN
1535-3893
DOI
10.1021/pr4002096
language
English
LU publication?
yes
id
d0ff0b81-d2f5-44b8-af03-a4505c102064 (old id 4318778)
date added to LUP
2014-03-03 08:00:40
date last changed
2019-01-06 05:00:09
@article{d0ff0b81-d2f5-44b8-af03-a4505c102064,
  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.},
  author       = {Pernemalm, Maria and De Petris, Luigi and Branca, Rui M. and Forshed, Jenny and Kanter, Lena and Soria, Jean-Charles and Girard, Philippe and Validire, Pierre and Pawitan, Yudi and van den Oord, Joost and Lazar, Vladimir and Påhlman, Sven and Lewensohn, Rolf and Lehtio, Janne},
  issn         = {1535-3893},
  keyword      = {NSCLC,adenocarcinoma,relapse,glycolysis,hypoxia,HIF1,ENO1,VDAC1,CTSD,Warburg,prognosis,peptide isoelectric focusing},
  language     = {eng},
  number       = {9},
  pages        = {3934--3943},
  publisher    = {The American Chemical Society},
  series       = {Journal of Proteome Research},
  title        = {Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism},
  url          = {http://dx.doi.org/10.1021/pr4002096},
  volume       = {12},
  year         = {2013},
}