title: Quantitative proteomics profiling of primary lung adenocarcinoma tumors reveals functional perturbations in tumor metabolism.
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 HIF1α 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.
authors.affiliation: Cancer Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. maria.pernemalm@ki.se
authors.forename: Maria
authors.initials: M
authors.lastname: Pernemalm
authors.forename: Luigi
authors.initials: L
authors.lastname: De Petris
authors.forename: Rui M
authors.initials: RM
authors.lastname: Branca
authors.forename: Jenny
authors.initials: J
authors.lastname: Forshed
authors.forename: Lena
authors.initials: L
authors.lastname: Kanter
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Philippe
authors.initials: P
authors.lastname: Girard
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
authors.forename: Joost
authors.initials: J
authors.lastname: van den Oord
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Janne
authors.initials: J
authors.lastname: Lehtiö
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D053555:Keratin-5 / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D025341:Principal Component Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C503940:KRT5 protein, human; D053555:Keratin-5; D020543:Proteome; D025521:Tumor Suppressor Proteins; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1; C533922:CTSD protein, human; D002402:Cathepsin D; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase