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

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.