Histopathological grading affects survival in patients with IDH-mutant grade II and grade III diffuse gliomas

Franceschi, Enrico; Tosoni, Alicia; Bartolini, Stefania; Minichillo, Santino; Mura, Antonella; Asioli, Sofia; Bartolini, Daniela; Gardiman, Marina Paola; Gessi, Marco; Ghimenton, Claudio; Giangaspero, Felice; Lanza, Giovanni; Marucci, Gianluca; Novello, Mariangela; Silini, Enrico Maria; Zunarelli, Elena; Paccapelo, Alexandro; Brandes, Alba Ariela

doi:10.1016/j.ejca.2020.06.018

Cited by 33 publications

(18 citation statements)

References 22 publications

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“…Among the malignant gliomas, there are lower grade gliomas (LGGs) which include grade II and grade III gliomas. Besides molecular characteristics, histopathological grade can also affect the prognosis of the LGG patients, leading to the enormous variability in survival outcomes [ 30 ]. It is, therefore, important to identify prognostic biomarkers of LGG.…”

Section: Discussionmentioning

confidence: 99%

CKS2 (CDC28 protein kinase regulatory subunit 2) is a prognostic biomarker in lower grade glioma: a study based on bioinformatic analysis and immunohistochemistry

Qiu

et al. 2021

Bioengineered

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Gliomas account for the highest cases of primary brain malignancies. Whereas previous studies have demonstrated the roles of CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) in various cancer types, its functions in lower grade gliomas (LGGs) remain elusive. This study aimed to profile the expression and functions of CKS2 in LGG. Multiple online databases such as The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), Gene Expression Profiling Interactive Analysis 2nd edition (GEPIA2), Tumor Immune Estimation Resource 2nd edition (TIMER2.0) as well as Gene Expression Omnibus (GEO) were used in this study. Immunohistochemistry (IHC) was performed to evaluate CKS2 protein expression. Our data demonstrated upregulation of CKS2 in LGG tissues at both mRNA and protein level, especially in grade III gliomas. Similarly, there was increased expression of CKS2 in isocitrate dehydrogenase 1 (IDH1) wildtype gliomas. In addition, increased DNA copy number and DNA hypomethylation might be associated with the upregulation of the CKS2 in LGG. Using the Kaplan-Meier survival analysis and the Cox regression analysis, CKS2 was shown to be independently associated with poor prognosis of LGG patients. Receiver operating characteristic (ROC) analysis revealed that CKS2 could effectively predict the 1-, 3-and 5-year survival rates of LGG patients. Enrichment analyses revealed that CKS2 was mainly involved in the regulation of the cell cycle in LGG. Taken together, our study demonstrated that CKS2 might be a candidate prognostic biomarker for LGG and could predict the survival rates of LGG patients.

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Section: Discussionmentioning

confidence: 99%

CKS2 (CDC28 protein kinase regulatory subunit 2) is a prognostic biomarker in lower grade glioma: a study based on bioinformatic analysis and immunohistochemistry

Qiu

et al. 2021

Bioengineered

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“…Different diffuse glioma types lead to different prognosis and treatment methods. Researchers showed that greater grading was associated with poorer prognosis and was an independent prognostic factor in IDH-mutant grade II and grade III gliomas ( 3 ). Gliomas grading and molecular characteristics all should be considered into patients’ management for improving prognosis ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses

et al. 2021

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Gliomas are among the most common intracranial tumors which originated from neuroepithelial cells. Increasing evidence has revealed that long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA module regulation and tumor-infiltrating immune cells play important regulatory roles in the occurrence and progression of gliomas. However, the precise underlying molecular mechanisms remain largely unknown. Data on gliomas in The Cancer Genome Atlas lack normal control samples; to overcome this limitation, we combined 665 The Cancer Genome Atlas glioma RNA sequence datasets with 188 Genotype-Tissue Expression normal brain RNA sequences to construct an expression matrix profile after normalization. We systematically analyzed the expression of mRNAs, lncRNAs, and miRNAs between gliomas and normal brain tissues. Kaplan–Meier survival analyses were conducted to screen differentially expressed mRNAs, lncRNAs, and miRNAs. A prognostic miRNA-related competitive endogenous RNA network was constructed, and the core subnetworks were filtered using 6 miRNAs, 3 lncRNAs, and 11 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the biological functions of significantly dysregulated mRNAs. Co-expression network analysis was performed to analyze and screen the core genes. Furthermore, single-sample Gene Set Enrichment Analysis and immune checkpoint gene expression analysis were performed, as co-expression analysis indicated immune gene dysregulation in glioma. Finally, the expression of representative dysregulated genes was validated in U87 cells at the transcriptional level, establishing a foundation for further research. We identified 7017 mRNAs, 437 lncRNAs, and 9 miRNAs that were differentially expressed in gliomas. Kaplan–Meier survival analysis revealed 5684 mRNAs, 61 lncRNAs, and 7 miRNAs with potential as prognostic signatures in patients with glioma. The hub subnetwork of the competing endogenous RNA network between PART1-hsa-mir-25-SLC12A5/TACC2/BSN/TLN2/ZDHHC8 was screened out. Gene co-expression network, single-sample Gene Set Enrichment Analysis, and immune checkpoint expression analysis demonstrated that tumor-infiltrating immune cells are closely related to gliomas. We identified novel potential biomarkers to predict survival and therapeutic targets for patients with gliomas based on a large-scale sample. Importantly, we filtered pivotal genes that provide valuable information for further exploration of the molecular mechanisms underlying glioma tumorigenesis and progression.

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“…We made this decision due to the conflicting currently contested role of tumor grade on prognosis estimation. Indeed, in our previous report, the tumor grade seemed to affect the prognosis of patients with glioma, while other studies did not confirm this finding [32][33][34][35].…”

Section: Discussionmentioning

confidence: 64%

IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

Franceschi¹,

Biase

Nunno³

et al. 2021

Diagnostics

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Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.

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Histopathological grading affects survival in patients with IDH-mutant grade II and grade III diffuse gliomas

Cited by 33 publications

References 22 publications

CKS2 (CDC28 protein kinase regulatory subunit 2) is a prognostic biomarker in lower grade glioma: a study based on bioinformatic analysis and immunohistochemistry

CKS2 (CDC28 protein kinase regulatory subunit 2) is a prognostic biomarker in lower grade glioma: a study based on bioinformatic analysis and immunohistochemistry

Molecular Features of Glioma Determined and Validated Using Combined TCGA and GTEx Data Analyses

IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

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