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The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

Published online by Cambridge University Press:  23 September 2014

Wenhao Wu
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Yongji Tian
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Hong Wan
Affiliation:
Department of Biochemistry, Beijing Neurosurgical Institute, Capital Medical University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Yongmei Song
Affiliation:
State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Junhua Li
Affiliation:
Department of Biochemistry, Beijing Neurosurgical Institute, Capital Medical University, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Liwei Zhang*
Affiliation:
Department of Neurosurgery, Beijing Tiantan Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
*
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing, 100050, P.R. China. email: zhangliweittyy@yahoo.com.cn
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Abstract

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Background:

The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.

Methods:

This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.

Results:

Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.

Conclusions:

Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

Contexte:

Le pronostic général des gliomes du tronc cérébral est très mauvais et le traitement actuel ne prolonge pas significativement la survie de ces patients. Il est donc important d'étudier les mécanismes de biologie moléculaire liés à leur apparition et à leur développement afin d'en améliorer le traitement. La voie de signalisation Wnt/β-caténine est étroitement associée à l'apparition et au développement de tumeurs. Cependant, on ignore sa relation aux gliomes du tronc cérébral.

Méthode:

Dans cette étude, nous avons utilisé le buvardage Western ainsi que des méthodes d'immunohistochimie pour détecter l'expression de composantes reliées à la voie de signalisation Wnt/β-caténine, telles Wnt-1, Wnt-2, β-caténine et C-myc, dans 6 cerveaux normaux et 24 gliomes du tronc cérébral et nous avons analysé la relation entre leur expression et les caractéristiques anatomo-cliniques des tumeurs.

Résultats:

Wnt-1 n'avait pas d'expression apparente dans les tissus cérébraux normaux et il n'y avait pas de différence significative entre les gliomes du tronc cérébral de haut grade et ceux de bas grade de malignité. L'expression de Wnt-2, de β-caténine et de C-myc dans les gliomes du tronc cérébral de haut grade était significativement plus élevée que dans ceux de bas grade et dans le tissu cérébral normal, et leur expression était corrélée de façon positive à l'expression de Ki-67. De plus, l'expression de Wnt-2 et de C-myc était associée de façon significative au pronostic des patients atteints de gliomes du tronc cérébral. Une expression augmentée de β-caténine avait tendance à être associée à une survie plus courte, mais la différence n'était pas significative au point de vue statistique.

Conclusions:

Il se peut que la voie de signalisation Wnt/β-caténine soit activée de façon anormale et joue un rôle important dans l'apparition et le développement des gliomes du tronc cérébral. Wnt-2, β-caténine et C-myc pourraient constituer des cibles de traitement du gliome du tronc cérébral.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2013

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