Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4318778
- author
- organization
- publishing date
- 2013
- 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 (ACS)
- external identifiers
-
- wos:000330147800011
- scopus:84883766689
- pmid:23902561
- 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
- 2016-04-01 10:55:56
- date last changed
- 2022-02-25 06:57:52
@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}}, keywords = {{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 (ACS)}}, 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}}, doi = {{10.1021/pr4002096}}, volume = {{12}}, year = {{2013}}, }