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PROTEOMICS REVEALS DIFFERENTIALLY REGULATED PATHWAYS WHEN COMPARING LOW-VERSUS HIGH-GRADE ASTROCYTOMAS

ABSTRACT: Astrocytic tumors are known for their high progression capacity and for high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from low to high-grade astrocytoma are already known, mRNA copies do not necessarily correlate with protein abundance and, therefore could shadow further comprehension about this tumor’s biology. This motivates us to seek for complementary strategies to study tumor progression at the protein level. Here we compare the proteomic profile of biopsies from patients with low-grade (diffuse, n=6) versus high-grade astrocytoma (anaplastic and glioblastomas, n =10), using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the low- and high-grade groups, respectively. Our results revealed seventy-four differentially abundant proteins (p < 0.01); we then shortlist those related to greater malignancy. We also describe molecular pathways distinctly activated in the two groups, such as differences in the organization of the extracellular matrix, decisive both in tumor invasiveness and in signaling for cell division, which, together with marked contrasts in energy metabolism, are determining factors in the speed of growth and dissemination of these neoplasms. The degradation pathways of GABA, enriched in the low-grade group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to high-grade tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Marlon D M Santos

LAB HEAD: Juliana de S. da G. Fischer

PROVIDER: PXD033782 | Pride | 2023-08-04

REPOSITORIES: pride

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			Action	DRS
	20191218_66219_Denildo_Sample26_1.raw	Raw
	20191218_66219_Denildo_Sample26_1.sqt	Other
	20191218_66219_Denildo_Sample26_2.raw	Raw
	20191218_66219_Denildo_Sample26_2.sqt	Other
	20191218_66619_Denildo_Sample31_1.raw	Raw

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PROTEOMICS REVEALS DIFFERENTIALLY REGULATED PATHWAYS WHEN COMPARING LOW-VERSUS HIGH-GRADE ASTROCYTOMAS

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