Open Data for Differential Network Analysis in Glioma

Jean-Quartier, Claire; Jeanquartier, Fleur; Holzinger, Andreas

doi:10.3390/ijms21020547

Cited by 9 publications

(5 citation statements)

References 91 publications

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“…Furthermore, we found decreased proliferation and cell cycle arrest of ZNF554-transfected cells, which might be due to the downregulation of several cyclin-dependent kinases (CDK2, CDK9, CDK10, CDK13, CDK17), and five (CCNC, CCND3, CCNE2, CCNG1, CCNG2) out of six cyclin genes. This is in strong concordance with recent studies, one showing the anti-glioma effect of CDK inhibitors already in preclinical/clinical use [45], the other finding several CDKs and cyclin genes amongst top hub nodes in glioma network analysis [46].…”

Section: Znf554 As a Potential Tumor Suppressor In Gliomassupporting

confidence: 91%

Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

Balogh

Reiniger

Hetey

et al. 2020

IJMS

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Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein subfamily, is predominantly expressed in the brain and placenta in humans. Recently, we unveiled that ZNF554 regulates trophoblast invasion during placentation and its decreased expression leads to the early pathogenesis of preeclampsia. Since ZNF proteins are immensely implicated in the development of several tumors including malignant tumors of the brain, here we explored the pathological role of ZNF554 in gliomas. We examined the expression of ZNF554 at mRNA and protein levels in normal brain and gliomas, and then we searched for genome-wide transcriptomic changes in U87 glioblastoma cells transiently overexpressing ZNF554. Immunohistochemistry of brain tissues in our cohort (n = 62) and analysis of large TCGA RNA-Seq data (n = 687) of control, oligodendroglioma, and astrocytoma tissues both revealed decreased expression of ZNF554 towards higher glioma grades. Furthermore, low ZNF554 expression was associated with shorter survival of grade III and IV astrocytoma patients. Overexpression of ZNF554 in U87 cells resulted in differential expression, mostly downregulation of 899 genes. The “PI3K-Akt signaling pathway”, known to be activated during glioma development, was the most impacted among 116 dysregulated pathways. Most affected pathways were cancer-related and/or immune-related. Congruently, cell proliferation was decreased and cell cycle was arrested in ZNF554-transfected glioma cells. These data collectively suggest that ZNF554 is a potential tumor suppressor and its decreased expression may lead to the loss of oncogene suppression, activation of tumor pathways, and shorter survival of patients with malignant glioma.

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Section: Znf554 As a Potential Tumor Suppressor In Gliomassupporting

confidence: 91%

Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

Balogh

Reiniger

Hetey

et al. 2020

IJMS

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“…Many such targets have been discovered with the application of high-throughput sequencing; however, inconsistencies exist between DEGs in different studies. 14 On the basis of previous work, we comprehensively analyzed hub genes associated with survival and prognosis in glioma, but which have rarely been studied or have been reported in other tumors but not in glioma, [15][16][17][18][19] using RRA and WGNA bioinformatics methods. A co-expression network previously constructed using WGCNA showed that some hub genes correlated with clinical traits of glioma samples in CGGA and TCGA datasets.…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and biological pathways in glioma via integrated bioinformatics analysis

Chen

Sun

et al. 2022

J Int Med Res

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Objective Glioma is the most common intracranial primary malignancy, but its pathogenesis remains unclear. Methods We integrated four eligible glioma microarray datasets from the gene expression omnibus database using the robust rank aggregation method to identify a group of significantly differently expressed genes (DEGs) between glioma and normal samples. We used these DEGs to explore key genes closely associated with glioma survival through weighted gene co-expression network analysis. We then constructed validations of prognosis and survival analyses for the key genes via multiple databases. We also explored their potential biological functions using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Results We selected DLGAP5, CDCA8, NCAPH, and CCNB2, as four genes that were abnormally up-regulated in glioma samples, for verification. They showed high levels of isocitrate dehydrogenase gene mutation and tumor grades, as well as good prognostic and diagnostic value for glioma. Their methylation levels were generally lower in glioma samples. GSEA and GSVA analyses suggested the genes were closely involved with glioma proliferation. Conclusion These findings provide new insights into the pathogenesis of glioma. The hub genes have the potential to be used as diagnostic and therapeutic markers.

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“…At present, the existence of an open database is very important. The complexity of cancer disease requires a large amount of data as a supporting basis, and the existence of an open database can accelerate related research and save researchers’ resources ( 16 ). Therefore, this retrospective study included histopathological slides of H&E-stained tissue samples from two cohorts of glioblastoma patients.…”

Section: Methodsmentioning

confidence: 99%

Computational pathology-based weakly supervised prediction model for MGMT promoter methylation status in glioblastoma

He,

Duan,

Dong

et al. 2024

Front. Neurol.

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IntroductionThe methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) is closely related to the treatment and prognosis of glioblastoma. However, there are currently some challenges in detecting the methylation status of MGMT promoters. The hematoxylin and eosin (H&E)-stained histopathological slides have always been the gold standard for tumor diagnosis.MethodsIn this study, based on the TCGA database and H&E-stained Whole slide images (WSI) of Beijing Tiantan Hospital, we constructed a weakly supervised prediction model of MGMT promoter methylation status in glioblastoma by using two Transformer structure models.ResultsThe accuracy scores of this model in the TCGA dataset and our independent dataset were 0.79 (AUC = 0.86) and 0.76 (AUC = 0.83), respectively.ConclusionThe model demonstrates effective prediction of MGMT promoter methylation status in glioblastoma and exhibits some degree of generalization capability. At the same time, our study also shows that adding Patches automatic screening module to the computational pathology research framework of glioma can significantly improve the model effect.

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Open Data for Differential Network Analysis in Glioma

Cited by 9 publications

References 91 publications

Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival

Identification of hub genes and biological pathways in glioma via integrated bioinformatics analysis

Computational pathology-based weakly supervised prediction model for MGMT promoter methylation status in glioblastoma

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