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Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas

Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from grade 2 to grade 4 astrocytoma are already known, mRNA copies do not necess...

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Autores principales: Verissimo, Denildo C. A., Camillo-Andrade, Amanda C., Santos, Marlon D. M., Sprengel, Sergio L., Zanine, Simone C., Borba, Luis A. B., Carvalho, Paulo C., da G. Fischer, Juliana de S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651032/
https://www.ncbi.nlm.nih.gov/pubmed/37967105
http://dx.doi.org/10.1371/journal.pone.0290087
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author Verissimo, Denildo C. A.
Camillo-Andrade, Amanda C.
Santos, Marlon D. M.
Sprengel, Sergio L.
Zanine, Simone C.
Borba, Luis A. B.
Carvalho, Paulo C.
da G. Fischer, Juliana de S.
author_facet Verissimo, Denildo C. A.
Camillo-Andrade, Amanda C.
Santos, Marlon D. M.
Sprengel, Sergio L.
Zanine, Simone C.
Borba, Luis A. B.
Carvalho, Paulo C.
da G. Fischer, Juliana de S.
author_sort Verissimo, Denildo C. A.
collection PubMed
description Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from grade 2 to grade 4 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 grade 2 (diffuse, n = 6) versus grade 4 astrocytomas (glioblastomas, n = 10) using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the 2- and 4-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 grade 2 group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to grade 4 tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups.
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spelling pubmed-106510322023-11-15 Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas Verissimo, Denildo C. A. Camillo-Andrade, Amanda C. Santos, Marlon D. M. Sprengel, Sergio L. Zanine, Simone C. Borba, Luis A. B. Carvalho, Paulo C. da G. Fischer, Juliana de S. PLoS One Research Article Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from grade 2 to grade 4 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 grade 2 (diffuse, n = 6) versus grade 4 astrocytomas (glioblastomas, n = 10) using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the 2- and 4-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 grade 2 group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to grade 4 tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups. Public Library of Science 2023-11-15 /pmc/articles/PMC10651032/ /pubmed/37967105 http://dx.doi.org/10.1371/journal.pone.0290087 Text en © 2023 Verissimo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Verissimo, Denildo C. A.
Camillo-Andrade, Amanda C.
Santos, Marlon D. M.
Sprengel, Sergio L.
Zanine, Simone C.
Borba, Luis A. B.
Carvalho, Paulo C.
da G. Fischer, Juliana de S.
Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title_full Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title_fullStr Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title_full_unstemmed Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title_short Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
title_sort proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651032/
https://www.ncbi.nlm.nih.gov/pubmed/37967105
http://dx.doi.org/10.1371/journal.pone.0290087
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