Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep 14;6(38):24535-24544.
doi: 10.1021/acsomega.1c02991. eCollection 2021 Sep 28.

The Big Picture of Glioblastoma Malignancy: A Meta-Analysis of Glioblastoma Proteomics to Identify Altered Biological Pathways

Anna K W Tribe  1 , Melanie J McConnell  1 , Paul H Teesdale-Spittle  1
Affiliations

The Big Picture of Glioblastoma Malignancy: A Meta-Analysis of Glioblastoma Proteomics to Identify Altered Biological Pathways

Anna K W Tribe et al. ACS Omega. .

Abstract

Glioblastoma is a highly malignant cancer with no effective treatment. It is vital to elucidate the mechanisms which drive glioblastoma in order to identify therapeutic targets. The differences in protein expression between glioblastoma, grade I-III glioma, and normal brain tissue reflect the functional alterations driving malignancy. However, proteomic analysis of glioblastoma has been hampered by the heterogeneity of glioblastoma and the variety of methodology used in its study. To reduce these inconsistencies, we performed a meta-analysis of the literature published since 2015, including 14 datasets from eight papers comparing the whole proteome of glioblastoma to normal brain or grade I-III glioma. We found that 154 proteins were commonly upregulated and 116 proteins were commonly downregulated in glioblastoma compared to normal brain. Meanwhile, 240 proteins were commonly upregulated and 125 proteins were commonly downregulated in glioblastoma compared to grade I-III glioma. Functional enrichment analysis revealed upregulation of proteins involved in mRNA splicing and the immune system and downregulation of proteins involved in synaptic signaling and glucose and glutamine metabolism. The identification of these altered biological pathways provides a basis for deeper investigation in the pursuit of an effective treatment for glioblastoma.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Flowchart of paper selection based on defined inclusion and exclusion criteria (see Methods).
Figure 2
Figure 2
Most significant parent terms in (A) Gene Ontology Biological Process domain (GO:BP) and (B) Reactome functional enrichment analysis of proteins downregulated in GBM compared to normal brain, ranked by the −log p value.
Figure 3
Figure 3
Most significant parent terms in (A) GO:BP and (B) Reactome functional enrichment analysis of proteins downregulated in GBM compared to LGG, ranked by the −log p value.
Figure 4
Figure 4
Most significant parent terms in (A) GO:BP and (B) Reactome functional enrichment analysis of proteins upregulated in GBM compared to normal brain, ranked by the −log p value.
Figure 5
Figure 5
Most significant parent terms in (A) GO:BP and (B) Reactome functional enrichment analysis of proteins upregulated in GBM compared to LGG, ranked by the −log p value.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ostrom Q. T.; Cioffi G.; Gittleman H.; Patil N.; Waite K.; Kruchko C.; Barnholtz-Sloan J. S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol. 2019, 21, v1–v100. 10.1093/neuonc/noz150. - DOI - PMC - PubMed
    1. Louis D. N.; Ohgaki H.; Wiestler O. D.; Cavenee W. K.; Burger P. C.; Jouvet A.; Scheithauer B. W.; Kleihues P. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol. 2007, 114, 97–109. 10.1007/s00401-007-0243-4. - DOI - PMC - PubMed
    1. Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways. Nature 2008, 455, 1061–1068. 10.1038/nature07385. - DOI - PMC - PubMed
    1. Verhaak R. G. W.; Hoadley K. A.; Purdom E.; Wang V.; Qi Y.; Wilkerson M. D.; Miller C. R.; Ding L.; Golub T.; Mesirov J. P.; Alexe G.; Lawrence M.; O’Kelly M.; Tamayo P.; Weir B. A.; Gabriel S.; Winckler W.; Gupta S.; Jakkula L.; Feiler H. S.; Hodgson J. G.; James C. D.; Sarkaria J. N.; Brennan C.; Kahn A.; Spellman P. T.; Wilson R. K.; Speed T. P.; Gray J. W.; Meyerson M.; Getz G.; Perou C. M.; Hayes D. N. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010, 17, 98–110. 10.1016/j.ccr.2009.12.020. - DOI - PMC - PubMed
    1. Wang Q.; Hu B.; Hu X.; Kim H.; Squatrito M.; Scarpace L.; deCarvalho A. C.; Lyu S.; Li P.; Li Y.; Barthel F.; Cho H. J.; Lin Y.-H.; Satani N.; Martinez-Ledesma E.; Zheng S.; Chang E.; Sauvé C.-E. G.; Olar A.; Lan Z. D.; Finocchiaro G.; Phillips J. J.; Berger M. S.; Gabrusiewicz K. R.; Wang G.; Eskilsson E.; Hu J.; Mikkelsen T.; DePinho R. A.; Muller F.; Heimberger A. B.; Sulman E. P.; Nam D.-H.; Verhaak R. G. W. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell 2017, 32, 42–56. 10.1016/j.ccell.2017.06.003. - DOI - PMC - PubMed