Genes of the Ubiquitin Proteasome System Qualify as Differential Markers in Malignant Glioma of Astrocytic and Oligodendroglial Origin.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35896929", "kind": "science-record", "revision": 5, "content_hash": "sha256:12edfeed7c364fd44d19453a726e4cc3279ef0802d6eca084ea0ab350668c511", "created_at": "2026-11-01T18:14:59Z", "updated_at": "2026-11-01T22:49:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genes of the Ubiquitin Proteasome System Qualify as Differential Markers in Malignant Glioma of Astrocytic and Oligodendroglial Origin.", "doi": "10.1007/s10571-022-01261-0", "pmid": "35896929", "authors": ["Jerry Vriend", "Thomas Klonisch"], "journal": "Cellular and molecular neurobiology", "year": 2023, "abstract": "We have mined public genomic datasets to identify genes coding for components of the ubiquitin proteasome system (UPS) that may qualify as potential diagnostic and therapeutic targets in the three major glioma types, astrocytoma (AS), glioblastoma (GBM), and oligodendroglioma (ODG). In the Sun dataset of glioma (GEO ID: GSE4290), expression of the genes UBE2S and UBE2C, which encode ubiquitin conjugases important for cell-cycle progression, distinguished GBM from AS and ODG. KEGG analysis showed that among the ubiquitin E3 ligase genes differentially expressed, the Notch pathway was significantly over-represented, whereas among the E3 ligase adaptor genes the Hippo pathway was over-represented. We provide evidence that the UPS gene contributions to the Notch and Hippo pathway signatures are related to stem cell pathways and can distinguish GBM from AS and ODG. In the Sun dataset, AURKA and TPX2, two cell-cycle genes coding for E3 ligases, and the cell-cycle gene coding for the E3 adaptor CDC20 were upregulated in GBM. E3 ligase adaptor genes differentially expressed were also over-represented for the Hippo pathway and were able to distinguish classic, mesenchymal, and proneural subtypes of GBM. Also over-expressed in GBM were PSMB8 and PSMB9, genes encoding subunits of the immunoproteasome. Our transcriptome analysis provides a strong rationale for UPS members as attractive therapeutic targets for the development of more effective treatment strategies in malignant glioma. Ubiquitin proteasome system and glioblastoma: E1-ubiquitin-activating enzyme, E2-ubiquitin-conjugating enzyme, E3-ubiquitin ligase. Ubiquitinated substrates of E3 ligases may be degraded by the proteasome. Expression of genes for specific E2 conjugases, E3 ligases, and genes for proteasome subunits may serve as differential markers of subtypes of glioblastoma.", "claims": [{"id": "claim-method", "statement": "Differential gene expression between the malignant gliomas studied (AS, GBM, ODG) and between the three GBM subtypes (classic, mesenchymal, and proneural) was determined by analysis of variance (ANOVA) through the R2 Genomics site.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35896929", "locator": "sections[2] \"Methods\" paragraph 3", "quote": "Differential gene expression between the malignant gliomas studied (AS, GBM, ODG) and between the three GBM subtypes (classic, mesenchymal, and proneural) was determined by analysis of variance (ANOVA) through the R2 Genomics site."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data referred to in this manuscript are publicly available at the R2 Genomics Analysis and Visualization Platform (http://r2.amc.nl) and GSE4290.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35896929", "locator": "sections[24] \"notes\" paragraph 1", "quote": "The data referred to in this manuscript are publicly available at the R2 Genomics Analysis and Visualization Platform (http://r2.amc.nl) and GSE4290."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ANOVA analysis of the public Sun glioma dataset identified differentially expressed E3 ligase and E3 ligase adaptor genes that distinguished GBM, AS, and ODG.", "kind": "quantitative", "target": {"value": 2.0, "unit": "correlation coefficient", "tolerance": null, "source": "A shortlist of differentially expressed genes coding for E3 ligases and E3 ligase adaptors distinguishing GBM, AS, and ODG was identified by ANOVA of log2 data using the Sun glioma dataset (Tumor – glioma) and the R2 Genomics Analysis and Visualization Platform."}, "evidence": [{"asset": "source:pmid:35896929", "locator": "sections[5] \"Expression of E3 Ligase Genes Distinguish GBM from AS and ODG and are Associated with Survival\" paragraph 2", "quote": "A shortlist of differentially expressed genes coding for E3 ligases and E3 ligase adaptors distinguishing GBM, AS, and ODG was identified by ANOVA of log2 data using the Sun glioma dataset (Tumor – glioma) and the R2 Genomics Analysis and Visualization Platform."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ANOVA analysis of the public Sun glioma dataset identified differentially expressed E3 ligase and E3 ligase adaptor genes that distinguished GBM, AS, and ODG.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35896929"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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