Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

Zhang, Yu; Long, Jianfei; Ren, Junwei; Huang, Xiang; Zhong, Ping; Wang, Bin

doi:10.3389/fonc.2021.731441

Cited by 18 publications

(19 citation statements)

References 171 publications

(249 reference statements)

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“…Among ether lysophospholipids, the primary member is the Platelet Activating Factor (PAF) [ 37 ], a potent effector of inflammation produced by basophils, which could be recruited at the tumor site. The enhanced level of ether lysophospholipids in schwannomas agreed with an inflammatory hallmark present in these tumors, as previously reported for vestibular schwannomas [ 38 , 39 ]. Pro-inflammatory cytokines, including TGF-β1, TNF-α, IL-1β, and IL-6, may be secreted by activated leukocytes, fibroblasts, and Schwann cells [ 39 ].…”

Section: Discussionsupporting

confidence: 88%

“…Neurosurgical procedures were carried out under general anesthesia and microscopic view. According to our institutional protocol for peripheral nerve surgery and the literature recommendations [ 9 , 10 , 38 ], intraoperative neurophysiological monitoring was performed when indicated to identify functioning fascicles and localize the safest entry point inside the tumor capsule. Immediately after excision, all tumor samples for lipidomic were cryopreserved and stored in liquid nitrogen at the Neurobiology laboratory according to standard operating procedures [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

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The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

Vetrano

Dei

Nazzi

et al. 2021

IJMS

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Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.

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Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

Vetrano

Dei

Nazzi

et al. 2021

IJMS

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“…The intensity of the NF-kB signaling pathway of intermediate monocytes was significantly higher than that of other clusters. Previous studies have shown that activated NF-κB is the mechanism responsible for the upregulated expression of p75NTR to promote the survival of Schwann cells ( Zhang et al, 2021 ). High NF-κB activity enhances hepatocyte growth factor (HGF) and the c-Met autocrine feedforward loop to promote tumor cell proliferation and increases the expression of prognostic factors in VS, such as matrix metalloproteinase 2 (MMP-2), MMP-9, MMP-14, COX-2, interleukin 1 (IL-1), IL-6, TNF- α ( Xu et al, 2019 ), and signal transduction transcriptional activator 1 (STAT1) ( Solinas et al, 2009 ), or the absolute tumor growth rate of VS ( Behling et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…It is worth noting that through the analysis of Schwann cell transcription factors, we found that Schwann cells may promote the proliferation of vestibular schwannoma by promoting vascular proliferation through transcription factor PKNOX1. It has been reported that the expression of VEGF, VEGFR-1/Flt, VEGFR-2/Flk, and coreceptor NP1 in VS tissue is significantly higher than that in normal vestibular nerve, suggesting that at least part of tumor growth is achieved by promoting angiogenesis ( Zhang et al, 2021 ). This is consistent with our research results.…”

Section: Discussionmentioning

confidence: 99%

Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma

Chu

Chen

Deng

et al. 2022

Front. Mol. Neurosci.

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In this study, based on three tumor samples obtained from patients with sporadic vestibular schwannoma, 32,011 cells were obtained by single-cell transcriptome sequencing, and 22,309 high-quality cells were obtained after quality control and double cells removal. Then, 18 cell clusters were obtained after cluster analysis, and each cluster was annotated as six types of cells. Afterward, an in-depth analysis was conducted based on the defined six cell clusters, including characterizing the functional characteristics of each cell subtype, describing the cell development and differentiation pathway, exploring the interaction between cells, and analyzing the transcriptional regulatory network within the clusters. Based on these four dimensions, various types of cells in sporadic vestibular schwannoma tumor tissues were described in detail. For the first time, we expanded on the functional state of cell clusters that have been reported and described Schwann cells in the peripheral nervous system, which have not been reported in previous studies. Combined with the data of sporadic vestibular schwannoma and normal tissues in the gene expression omnibus (GEO) database, the candidate biomarkers of sporadic vestibular schwannoma were explored. Overall, this study described the single-cell map of sporadic vestibular schwannoma for the first time, revealing the functional state and development trajectory of different cell types. Combined with the analysis of data in the GEO database and immunohistochemical verification, it was concluded that HLA-DPB1 and VSIG4 may be candidate biomarkers and potential therapeutic targets for patients with sporadic vestibular schwannoma.

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“…ErbB receptors were activated in both sporadic and NF2-related VSs, and EGFR expression levels correlated with Sch size [ 26 ]. Furthermore, EGF was upregulated in NF2-related VS but not in sporadic VS, suggesting that an EGFR inhibitor might have efficacy in NF2 patients [ 27 , 28 ].…”

Section: Protein-kinase-related Pathwaymentioning

confidence: 99%

A Critical Overview of Targeted Therapies for Vestibular Schwannoma

Tamura

Toda

2022

IJMS

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Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.

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Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

Cited by 18 publications

References 171 publications

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma

A Critical Overview of Targeted Therapies for Vestibular Schwannoma

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