Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

Roesler, Rafaël; Souza, Bárbara Kunzler; Isolan, Gustavo Rassier

doi:10.3390/ijms222111352

Cited by 3 publications

(4 citation statements)

References 88 publications

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“…In addition, a violin plot analysis was performed on a dataset of 42 invasive meningioma tumor samples. Although the analysis revealed overall similar gene expression across different ErbB receptor family members, higher levels of ErbB2 (HER2) and ErbB3 (HER3) gene expression were observed in meningioma patients compared to all other members of the ErbB receptor family [ 44] . However, these studies do not indicate a trend relationship between ErbB3 and WHO grade, and the relevant studies are also less reported.…”

Section: Distribution Differences Of Hub Genes Under Who Classi Catio...mentioning

confidence: 86%

Analysis of clinical features, prognosis and potential target genes of refractory meningioma-- Research based on multiple databases

Li,

Zhu

et al. 2023

Preprint

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Objective: Analyzing SEER database data on malignant meningiomas, we explored high-risk factors for refractory meningiomas (RMs). Additionally, we analyzed GEO database genes across WHO grades to identify key genes and malignant risk factors for RMs. Immunohistochemical analysis was performed on WHO grade meningiomas' pathological specimens to verify hub gene expression differences. Methods: We included clinical cases of malignant meningiomas diagnosed in the SEER database. GEO database provided a gene expression profile dataset of 252 samples. Significant expression differences yielded screened genes, constructing a PPI network and identifying common hub genes. Hub gene-WHO classification correlation was assessed. A single center collected 38 meningioma samples grouped by WHO grade. Immunohistochemistry confirmed hub gene expressions. Results: SEER study: Multivariate COX analysis revealed age (P < 0.001), sex (P=0.071), chemotherapy (P < 0.001), and tumor size (P=0.003) as statistically significant prognostic factors. Gene database analysis: Differential genes ErbB3 and EGFR were identified; Progesterone and estrogen receptors PR and ER were also included, with distinct expressions across WHO grades (P < 0.001), except for ER. Pathological data study: EGFR correlated positively with WHO grade (r=0.396, P=0.014). ErbB3 (r=-0.487, p=0.002), ER (r=-0.396, P= 0.002), and egfr (r=-0.396, P=0.014) correlated negatively. nPR (r=-0.519, P < 0.001) and PR (r=-0.218, p=0.189) correlated negatively. nEGFR (r=-0.061, p=0.717) were not significant. ER (r=-0.316, P=0.065) and nPR (r=-0.443, P=0.008) correlated negatively with recurrence. Conclusion: EGFR, ErbB3, ER, and nPR might be potential RM diagnostic and treatment targets. mPR distribution discrepancies may hold diagnostic and therapeutic importance under new classifications or definitions.

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Section: Distribution Differences Of Hub Genes Under Who Classi Catio...mentioning

confidence: 86%

Analysis of clinical features, prognosis and potential target genes of refractory meningioma-- Research based on multiple databases

Li,

Zhu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Nevertheless, future therapeutic approaches may be based on identification of potential unique molecular targets. As most growth factor receptors and tyrosine kinases are expressed in human meningiomas with subsequent activation of several intracellular signalling pathways (26,31), molecular targeted therapies including tyrosine kinase inhibitors have emerged (26,31,38,42). In this regard, pilot studies with ErbB tyrosine kinase inhibitors have largely been ineffective, mostly due to acquired resistance (38).…”

Section: Discussionmentioning

confidence: 99%

“…Activated ErbB receptors trigger a cascade of fundamental downstream signalling pathways, such as the Ras-ERK, P13K-Akt, PLC-γ1, STAT1, and Src pathways (14,17,18), which are involved in many essential cellular processes, including survival, differentiation, proliferation, metabolism, adhesion, motility, and angiogenesis (14,15,17,18). Hence, aberrant ErbB expression is implicated in many human malignancies and has shown diagnostic, prognostic, and therapeutic significance (14,16,17,19), whereas in human meningiomas the clinical significance is more ambiguous (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological significance of concurrent ErbB receptor expression in human meningioma

Torp,

Arnli,

Scheie

2023

Mol Clin Oncol

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In general, human meningiomas grow slowly and have a favourable prognosis; however, some are prone to recur despite their benign histology. Therefore, knowledge of their tumour biology is essential to determine objective biomarkers that can identify cases with an increased risk for recurrence and to generate effective treatment options. Thus, studies on the epidermal growth factor receptor (EGFR) family, comprising ErbB1/EGFR, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, are important. We have recently published papers on the expression of each of these receptor proteins in human meningiomas. The present study aimed to assess the clinicopathological significance of their concurrent expression. A total of 185 grade 1 and 2 meningiomas with robust clinical data underwent immunohistochemical analyses with antibodies against the aforementioned receptors. All meningiomas exhibited upregulation of these receptor proteins relative to normal meninges. In addition, the expression of phosphorylated/activated ErbB1/EGFR1 and phosphorylated/activated ErbB2/HER2 was significantly associated with histological malignancy grade and prognosis, respectively. The concurrent upregulation of ErbB receptors in human meningioma supports their fundamental role in the tumourigenesis of these tumours, and they could thus be exploited in diagnostics, prognosis, and ultimately, in targeted clinical interventions.

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“…Phosphorylation modification of proteins based on tyrosine kinase plays a crucial role in the response to stimuli and the regulation of biological processes in cell [9][10][11]. In MSC, the proliferation and multi-differentiation of cells are also significantly influenced by the activity of tyrosine kinase, so strategies to enhance the regeneration ability of MSC through small molecule preparations targeting tyrosine kinases are receiving increasing attention [12, Ivyspring International Publisher 13].…”

Section: Introductionmentioning

confidence: 99%

Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals

Jia,

Zhang,

Sun

et al. 2023

Int. J. Med. Sci.

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Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.

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Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

Cited by 3 publications

References 88 publications

Analysis of clinical features, prognosis and potential target genes of refractory meningioma-- Research based on multiple databases

Analysis of clinical features, prognosis and potential target genes of refractory meningioma-- Research based on multiple databases

Clinicopathological significance of concurrent ErbB receptor expression in human meningioma

Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals

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