CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion

Cardoso, Lais Cavalca; Soares, Roseli da Silva; Laurentino, Talita de Sousa; Lerário, Antônio Marcondes; Marie, Suely Kazue Nagahashi; Oba-Shinjo, Sueli Mieko

doi:10.3390/ijms20051137

Cited by 19 publications

(11 citation statements)

References 52 publications

(56 reference statements)

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“…However, to the best of our knowledge, no international guidelines were established on how to standardize the scoring and interpretation of CD99 immunoreactivity in EwS. In addition, CD99 is highly expressed in several other cancer types [48][49][50], and its specificity for EwS among differential diagnoses was found to be remarkably low in our previous study (17% at a cut-off of 2 [27]).…”

Section: Ihc For Cd99 and Fish For Ewsr1 Break-apart Are Not Fully Sumentioning

confidence: 86%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

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Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.

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Section: Ihc For Cd99 and Fish For Ewsr1 Break-apart Are Not Fully Sumentioning

confidence: 86%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

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“…Surprisingly, although most of M1 genes showed positive correlations, CD99 , MTRNR2L1 , and MTRNR2L8 were negatively correlated with others. As it has been widely reported that overexpression of CD99 could increase the migration and invasiveness of GBM cells ( Seol et al, 2012 ; Cardoso et al, 2019 ), we deduced that although CD99 and other invasion-associated PCGs play key roles in regulating tumor cell invasion, their mediated mechanisms were distinct and redundant, resulting in their mutually exclusive expression patterns. Moreover, combining our previous work for characterization of cell clusters and construction of progression trajectory, we further confirmed the contribution of M1 to GBM invasion as M1 genes showed relatively high expression in cell clusters with high EMT and invasive scores.…”

Section: Discussionmentioning

confidence: 86%

Dissecting the Invasion-Associated Long Non-coding RNAs Using Single-Cell RNA-Seq Data of Glioblastoma

et al. 2021

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Glioblastoma (GBM) is characterized by rapid and lethal infiltration of brain tissue, which is the primary cause of treatment failure and deaths for GBM. Therefore, understanding the molecular mechanisms of tumor cell invasion is crucial for the treatment of GBM. In this study, we dissected the single-cell RNA-seq data of 3345 cells from four patients and identified dysregulated genes including long non-coding RNAs (lncRNAs), which were involved in the development and progression of GBM. Based on co-expression network analysis, we identified a module (M1) that significantly overlapped with the largest number of dysregulated genes and was confirmed to be associated with GBM invasion by integrating EMT signature, experiment-validated invasive marker and pseudotime trajectory analysis. Further, we denoted invasion-associated lncRNAs which showed significant correlations with M1 and revealed their gradually increased expression levels along the tumor cell invasion trajectory, such as VIM-AS1, WWTR1-AS1, and NEAT1. We also observed the contribution of higher expression of these lncRNAs to poorer survival of GBM patients. These results were mostly recaptured in another validation data of 7930 single cells from 28 GBM patients. Our findings identified lncRNAs that played critical roles in regulating or controlling cell invasion and migration of GBM and provided new insights into the molecular mechanisms underlying GBM invasion as well as potential targets for the treatment of GBM.

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“…Within the networks, notably, CD99 was reported as physically interactive with TRIP13 (edge weight 6.33). CD99 is a glycosylated transmembrane protein frequently highly expressed in malignant glioma with marked effects on the migration, invasion and metastasis of tumor cells [ 56 ]. In addition, CD99 may rearrange the actin cytoskeleton and has been reported to be involved in regulating cell differentiation, adhesion and migration of immune cells [ 57 , 58 ].…”

Section: Resultsmentioning

confidence: 99%

Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker

Chen

Lin

et al. 2021

Cancers

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The prognosis of malignant gliomas such as glioblastoma multiforme (GBM) has remained poor due to limited therapeutic strategies. Thus, it is pivotal to determine prognostic factors for gliomas. Thyroid Receptor Interacting Protein 13 (TRIP13) was found to be overexpressed in several solid tumors, but its role and clinical significance in gliomas is still unclear. Here, we conducted a comprehensive expression analysis of TRIP13 to determine the prognostic values. Gene expression profiles of the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and GSE16011 dataset showed increased TRIP13 expression in advanced stage and worse prognosis in IDH-wild type lower-grade glioma. We performed RT-PCR and Western blot to validate TRIP13 mRNA expression and protein levels in GBM cell lines. TRIP13 co-expressed genes via database screening were regulated by essential cancer-related upstream regulators (such as TP53 and FOXM1). Then, TCGA analysis revealed that more TRIP13 promoter hypomethylation was observed in GBM than in low-grade glioma. We also inferred that the upregulated TRIP13 levels in gliomas could be regulated by dysfunction of miR-29 in gliomas patient cohorts. Moreover, TRIP13-expressing tumors not only had higher aneuploidy but also tended to reduce the ratio of CD8+/Treg, which led to a worse survival outcome. Overall, these findings demonstrate that TRIP13 has with multiple functions in gliomas, and they may be crucial for therapeutic potential.

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CD99 Expression in Glioblastoma Molecular Subtypes and Role in Migration and Invasion

Cited by 19 publications

References 52 publications

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Dissecting the Invasion-Associated Long Non-coding RNAs Using Single-Cell RNA-Seq Data of Glioblastoma

Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker

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