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Quantitative Proteomic Analysis of Meningiomas for the Identification of Surrogate Protein Markers

View Article: PubMed Central - PubMed

ABSTRACT

Meningiomas are the most common non-glial tumors of the brain and spine. Pathophysiology and definite histological grading of meningiomas are frequently found to be deceptive due to their unusual morphological features and locations. Here for the first time we report a comprehensive serum proteomic analysis of different grades of meningiomas by using multiple quantitative proteomic and immunoassay-based approaches to obtain mechanistic insights about disease pathogenesis and identify grade specific protein signatures. In silico functional analysis revealed modulation of different vital physiological pathways including complement and coagulation cascades, metabolism of lipids and lipoproteins, immune signaling, cell growth and apoptosis and integrin signaling in meningiomas. ROC curve analysis demonstrated apolipoprotein E and A-I and hemopexin as efficient predictors for meningiomas. Identified proteins like vimentin, alpha-2-macroglobulin, apolipoprotein B and A-I and antithrombin-III, which exhibited a sequential increase in different malignancy grades of meningiomas, could serve as potential predictive markers.

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Schematic representation of the experimental strategy for proteomic analysis of alterations in the human serum proteome in different grades of human meningiomas (Drawn by the authors: S.S1 & S.R.).
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f1: Schematic representation of the experimental strategy for proteomic analysis of alterations in the human serum proteome in different grades of human meningiomas (Drawn by the authors: S.S1 & S.R.).

Mentions: This study aims to investigate alterations in the human serum proteome in different grades of human meningiomas; grade I (benign), grade II (atypical) and grade III (anaplastic) to obtain insights about disease pathogenesis and identify grade specific surrogate protein markers. For comparative proteomic analysis three complementary quantitative proteomic approaches; 2D-differential in gel electrophoresis (2D-DIGE) followed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and isobaric tags for relative and absolute quantitation (iTRAQ)-based and label-free quantitative proteomics in combination with electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) LC/MS-MS were employed. The results obtained from these complementary proteomic techniques were validated by ELISA and western blotting (Figure 1). The differentially expressed serum proteins (p < 0.05) identified in different grades of meningiomas were subjected to functional pathway analysis. Different software like protein analysis through evolutionary relationships (PANTHER), database for annotation, visualization and integrated discovery (DAVID), and GeneTrail functional annotation tools were employed to understand their biological context, involvement in various physiological pathways and association with disease pathophysiology. Functional pathway analysis revealed the modulation of different vital physiological pathways, including complement and coagulation cascades, metabolism of lipids and lipoproteins, signaling in immune system, cell growth and apoptosis, and integrin signaling in meningiomas. To the best of our knowledge, this is the first comprehensive investigation describing serum proteomic alterations in different grades of human meningiomas. Our findings may open up new opportunities for the early detection and prognosis of human meningiomas and provide better understanding of the underlying mechanism of the disease pathogenesis and tumour progression.


Quantitative Proteomic Analysis of Meningiomas for the Identification of Surrogate Protein Markers
Schematic representation of the experimental strategy for proteomic analysis of alterations in the human serum proteome in different grades of human meningiomas (Drawn by the authors: S.S1 & S.R.).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382771&req=5

f1: Schematic representation of the experimental strategy for proteomic analysis of alterations in the human serum proteome in different grades of human meningiomas (Drawn by the authors: S.S1 & S.R.).
Mentions: This study aims to investigate alterations in the human serum proteome in different grades of human meningiomas; grade I (benign), grade II (atypical) and grade III (anaplastic) to obtain insights about disease pathogenesis and identify grade specific surrogate protein markers. For comparative proteomic analysis three complementary quantitative proteomic approaches; 2D-differential in gel electrophoresis (2D-DIGE) followed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and isobaric tags for relative and absolute quantitation (iTRAQ)-based and label-free quantitative proteomics in combination with electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) LC/MS-MS were employed. The results obtained from these complementary proteomic techniques were validated by ELISA and western blotting (Figure 1). The differentially expressed serum proteins (p < 0.05) identified in different grades of meningiomas were subjected to functional pathway analysis. Different software like protein analysis through evolutionary relationships (PANTHER), database for annotation, visualization and integrated discovery (DAVID), and GeneTrail functional annotation tools were employed to understand their biological context, involvement in various physiological pathways and association with disease pathophysiology. Functional pathway analysis revealed the modulation of different vital physiological pathways, including complement and coagulation cascades, metabolism of lipids and lipoproteins, signaling in immune system, cell growth and apoptosis, and integrin signaling in meningiomas. To the best of our knowledge, this is the first comprehensive investigation describing serum proteomic alterations in different grades of human meningiomas. Our findings may open up new opportunities for the early detection and prognosis of human meningiomas and provide better understanding of the underlying mechanism of the disease pathogenesis and tumour progression.

View Article: PubMed Central - PubMed

ABSTRACT

Meningiomas are the most common non-glial tumors of the brain and spine. Pathophysiology and definite histological grading of meningiomas are frequently found to be deceptive due to their unusual morphological features and locations. Here for the first time we report a comprehensive serum proteomic analysis of different grades of meningiomas by using multiple quantitative proteomic and immunoassay-based approaches to obtain mechanistic insights about disease pathogenesis and identify grade specific protein signatures. In silico functional analysis revealed modulation of different vital physiological pathways including complement and coagulation cascades, metabolism of lipids and lipoproteins, immune signaling, cell growth and apoptosis and integrin signaling in meningiomas. ROC curve analysis demonstrated apolipoprotein E and A-I and hemopexin as efficient predictors for meningiomas. Identified proteins like vimentin, alpha-2-macroglobulin, apolipoprotein B and A-I and antithrombin-III, which exhibited a sequential increase in different malignancy grades of meningiomas, could serve as potential predictive markers.

No MeSH data available.


Related in: MedlinePlus