关键词: TAZ YAP1 astrocytoma low grade glioma oligodendroglioma

Mesh : Humans YAP-Signaling Proteins / metabolism Astrocytoma / metabolism genetics pathology mortality Adaptor Proteins, Signal Transducing / metabolism genetics Female Male Transcription Factors / genetics metabolism Brain Neoplasms / metabolism mortality genetics pathology Middle Aged Adult Neoplasm Grading Oligodendroglioma / genetics metabolism pathology mortality Phosphoproteins / metabolism genetics Aged Prognosis Gene Expression Regulation, Neoplastic Biomarkers, Tumor / metabolism genetics Transcriptional Coactivator with PDZ-Binding Motif Proteins Trans-Activators / genetics metabolism Young Adult

来  源:   DOI:10.21873/anticanres.17113

Abstract:
OBJECTIVE: Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma.
METHODS: A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on \"brain lower grade glioma\". mRNA expression rates were used to validate our findings on survival analysis.
RESULTS: Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data.
CONCLUSIONS: High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.
摘要:
目的:多形性胶质母细胞瘤(GBM)是最致命的脑癌类型之一,由于其侵袭性和缺乏有效的治疗选择,中位生存期仅为12个月。星形细胞瘤和少突胶质细胞瘤被归类为低级别胶质瘤(LGG),并有可能发展为继发性GBM。YAP1和TAZ是hippo途径的转录共激活因子,通过控制细胞增殖和分化在肿瘤发生中起重要作用。这项研究的目的是分析YAP1和TAZ是否影响星形细胞瘤和少突胶质细胞瘤患者的生存。
方法:使用实时PCR分析了总共22例星形细胞瘤患者样品和11例少突胶质细胞瘤样品。我们利用了来自癌症基因组图谱(TCGA)的开放获取数据,重点是“低度脑胶质瘤”。mRNA表达率用于验证我们在生存分析中的发现。
结果:YAP1在星形细胞瘤中的表达是少突胶质细胞瘤的两倍,而TAZ没有差异。在少突胶质细胞瘤中,TAZ在复发肿瘤中的表达高于原发性肿瘤。具有高YAP1表达的星形细胞瘤患者的总生存期明显短于具有较低表达的患者(中位生存期161vs.86个月,p=0.0248)。这些发现通过TCGA数据的生存分析得到了验证。
结论:高YAP1表达显示与LGG患者总生存期较差高度相关。YAP1在星形细胞瘤中的表达水平高于少突胶质细胞瘤。
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