Abstract
BackgroundWe obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins). There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system.MethodsThe Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses.ResultsFor the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a pituitary control related to gene expression and cellular development, and no canonical toxicity pathways were identified.ConclusionsThis pathway network analysis demonstrated that mitochondrial dysfunction, oxidative stress, cell-cycle dysregulation, and the MAPK-signaling abnormality are significantly associated with a pituitary adenoma. These pathway-network data provide new insights into the molecular mechanisms of human pituitary adenoma pathogenesis, and new clues for an in-depth investigation of pituitary adenoma and biomarker discovery.
Highlights
We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins)
Pathway networks derived from protein-mapping data Among the 154 identifiers that represented the 111 proteins that were identified from human pituitary adenoma tissue, 147 identifiers were mapped to the corresponding molecules, except for 7 identifiers (Additional file 1, Table S1)
The Fisher's exact test that is contained in the Ingenuity Pathway Analysis (IPA) program was used to uncover any statistically significant pathways or networks with a significance level of 0.05. For those four protein datasets in this study: we identified 37 significant canonical pathways and 6 pathway networks derived from our proteinmapping dataset, 9 significant canonical pathways and 3 pathway networks derived from our comparative proteomic dataset, 12 significant canonical pathways and 1 pathway network derived from our qualitative nitroproteomic dataset in adenomas, and 12 significant canonical pathways and 1 pathway network derived from our qualitative nitroproteomic dataset in controls
Summary
We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins). There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Our long-term goals for this human pituitary study are to clarify the molecular mechanisms that are involved in pituitary adenoma pathogenesis and to discover tumor biomarkers Towards those ends, a series of pituitary adenoma proteomic expression data, which include 111 proteins identified from a human pituitary non-functional adenoma tissue [1], 56 differentially expressed proteins (DEP's) from human pituitary nonfunctional adenoma tissues and from prolactinoma tissues [2,3], nine nitroproteins and three nitroprotein-protein complexes from a human pituitary nonfunctional adenoma tissue [4], and eight nitroproteins from a pituitary control tissue [5,6], were analyzed. IPA can identify statistically significant signaling pathway networks by analyzing the -omic data in those numerous canonical-pathway databases
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