VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma

Wen Chin Weng, Kuan Hung Lin, Pei Yi Wu, Ya Hsuan Ho, Yen Lin Liu, Bo Jeng Wang, Chien Chin Chen, Yueh Chien Lin, Yung Feng Liao, Wang Tso Lee, Wen Ming Hsu, Hsinyu Lee

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Abstract

Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients' samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB.

Original languageEnglish
Article number11212
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Neuroblastoma
Vascular Endothelial Growth Factor A
Neoplasms
Heterografts
GAP-43 Protein
Messenger RNA
Angiogenesis Inducing Agents
Differentiation Antigens
Microvessels
Cell Differentiation
Carcinogenesis
Survival Rate

ASJC Scopus subject areas

  • General

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VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma. / Weng, Wen Chin; Lin, Kuan Hung; Wu, Pei Yi; Ho, Ya Hsuan; Liu, Yen Lin; Wang, Bo Jeng; Chen, Chien Chin; Lin, Yueh Chien; Liao, Yung Feng; Lee, Wang Tso; Hsu, Wen Ming; Lee, Hsinyu.

In: Scientific Reports, Vol. 7, No. 1, 11212, 01.12.2017.

Research output: Contribution to journalArticle

Weng, Wen Chin ; Lin, Kuan Hung ; Wu, Pei Yi ; Ho, Ya Hsuan ; Liu, Yen Lin ; Wang, Bo Jeng ; Chen, Chien Chin ; Lin, Yueh Chien ; Liao, Yung Feng ; Lee, Wang Tso ; Hsu, Wen Ming ; Lee, Hsinyu. / VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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abstract = "Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients' samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB.",
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AU - Wang, Bo Jeng

AU - Chen, Chien Chin

AU - Lin, Yueh Chien

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AU - Lee, Wang Tso

AU - Hsu, Wen Ming

AU - Lee, Hsinyu

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