Multipronged quantitative proteomic analyses indicate modulation of various signal transduction pathways in human meningiomas

Abstract

Meningiomas (MGs) are frequent tumors of the CNS originating from the meningeal layers of the spinal cord and the brain. In this study, comparative tissue proteomic analysis of low and high grades of MGs was performed by using iTRAQ-based quantitative proteomics in combination with ESI-quadrupole-TOF and Q-Exactive MS, and results were validated by employing ELISA. Combining the results obtained from two MS platforms, we were able to identify overall 4308 proteins (1% false discover rate), among which 2367 exhibited differential expression (more than and equal to 2 peptide and ≥ 1.5-fold in at least one grade) in MGs. Several differentially expressed proteins were found to be associated with diverse signaling pathways, including integrin, Wnt, Ras, epidermal growth factor receptor, and FGR signaling. Proteins, such as vinculin or histones, which act as the signaling activators to initiate multiple signaling pathways, were found to be upregulated in MGs. Quite a few candidates, such as protein S-100A6, aldehyde dehydrogenase mitochondrial, AHNAK, cytoskeleton-associated protein 4, and caveolin, showed sequential increase in low- and high-grade MGs, whereas differential expressions of collagen alpha-1 (VI), protein S100-A9, 14 kDa phosphohistidine phosphatase, or transgelin-2 were found to be grade specific. Our findings provide new insights regarding the association of various signal transduction pathways in MG pathogenesis and may introduce new opportunities for the early detection and prognosis of MGs.

Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target

“…A list of the significant differentially expressed proteins is summarized in Table S2. The top three upregulated include the fructose-bisphosphate aldolase C (ALDOC), the proteasome subunit beta type-5 (PSMB5) and transgelin (TAGLN), the latter identified also in previous studies (Sharma et al, 2015). All upregulated proteins were grouped based on protein class and are represented by a pie chart (Fig.…”

“…2E). Among the most interesting phospho-proteins identified were transgelin-2 (TAGLN2), previously found overexpressed in meningioma (Sharma et al, 2015); calcyclin binding protein (CACYBP), that can act as either an oncogene or a tumour suppressor depending on the type of cancer (Topolska-Wos et al, 2016); Deltex 3 like E3 ubiquitin ligase (DTX3L), able to modulate DNA damage responses rendering cancer cells resistant to certain chemotherapy drugs (Thang et al, 2015). Interestingly, there were several phospho-proteins identified as downregulated that are related to organization of the cytoskeleton like Junction Plakoglobin (JUP), with a Log 2 FC = − 20.663.…”

“…Recently Sharma and colleagues performed comparative proteomic analysis on different grades of meningiomas to investigate alterations in the meningioma tissue and in the human serum of meningioma patients compared to normal brain tissue. They identified several deregulated proteins including transgelin-2 and caveolin in tissue, plus apoliopoproteins A and E in serum (Sharma et al, 2014, Sharma et al, 2015). …”

MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

“…In meningiomas, E-cadherin expression is negatively correlated with WHO grade and invasion [29], while vimentin is increased with higher malignancy grades [30]. Downregulation of miR-200a, which was found in benign meningiomas compared to arachnoidal tissue, leads to an increased protein level of its direct targets i.e.…”

Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

“…Two different types of mass spectrometer, Agilent 6550 Q-TOF and Thermo Scientific Q-Exactive were used to analyze iTRAQ-labeled samples. Technical details for the mass spectrometric analysis, data acquisition and analysis have been reported previously [14,15]. In brief, data was acquired from an Agilent 6550 iFunnel Q-TOF LC MS/MS instrument (Agilent Technologies, USA) in a positive ion mode, monitored by Mass Hunter acquisition software.…”