Department of Neurosurgery, The 309th Hospital of PLA, Beijing, People's Republic of China.
Clin Exp Med. 2011 Jun;11(2):105-12. doi: 10.1007/s10238-010-0110-9. Epub 2010 Aug 31.
Gliomas are the most common primary intracranial tumors. Understanding the molecular basis of gliomas' progression is required to develop more effective therapies. The Wnt/β-catenin signaling cascade is an important signal transduction pathway in human cancers. Although, overactivation of this pathway is a hallmark of several forms of cancer, little is known about its role in human gliomas. Here, we aimed to determine the clinical significance of Wnt/β-catenin pathway components in gliomas. Immunohistochemical staining was performed to detect the expression patterns of Wnt1, β-catenin and Cyclin D1 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Cytoplasmic staining pattern of Wnt1, membranous, cytoplasmic and nuclear accumulation of β-catenin, and nuclear localization of Cyclin D1 were demonstrated by immunohistochemical staining. The Wnt1 expression significantly correlated with the expression of Cyclin D1 (P < 0.0001). The ratio of tumors with a cytoplasmic-nuclear pattern or a cytoplasmic pattern of β-catenin was significantly higher in Wnt1-positive (P < 0.01) and Cyclin D1-positive (P < 0.01) tumors than in Wnt1-negative and Cyclin D1-negative tumors, respectively. The protein expression levels of Wnt1, β-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas. Furthermore, Wnt1, cytoplasmic-nuclear β-catenin and Cyclin D1 status were all the independent prognostic factors for glioma patients (P = 0.01, 0.007 and 0.005, respectively). These results provide convincing evidence that the Wnt/β-catenin pathway correlated closely with the progression of gliomas and might be a novel prognostic marker for this neoplasm.
神经胶质瘤是最常见的原发性颅内肿瘤。为了开发更有效的治疗方法，需要了解神经胶质瘤进展的分子基础。Wnt/β-catenin 信号级联是人类癌症中重要的信号转导途径。尽管该途径的过度激活是几种癌症的标志，但人们对其在人类神经胶质瘤中的作用知之甚少。在这里，我们旨在确定 Wnt/β-catenin 通路成分在神经胶质瘤中的临床意义。通过免疫组织化学染色检测 96 例原发性神经胶质瘤患者活检中 Wnt1、β-catenin 和 Cyclin D1 的表达模式。进行 Kaplan-Meier 生存和 Cox 回归分析评估患者的预后。通过免疫组织化学染色显示 Wnt1 的细胞质染色模式、β-catenin 的膜质、细胞质和核积累以及 Cyclin D1 的核定位。Wnt1 的表达与 Cyclin D1 的表达显著相关（P<0.0001）。在 Wnt1 阳性（P<0.01）和 Cyclin D1 阳性（P<0.01）肿瘤中，β-catenin 的细胞质-核模式或细胞质模式的肿瘤比例明显高于 Wnt1 阴性和 Cyclin D1 阴性肿瘤。Wnt1、β-catenin 和 Cyclin D1 的蛋白表达水平均与神经胶质瘤患者的 Karnofsky 表现量表（KPS）评分和世界卫生组织（WHO）分级呈正相关。此外，Wnt1、细胞质-核 β-catenin 和 Cyclin D1 状态均是神经胶质瘤患者的独立预后因素（P=0.01、0.007 和 0.005）。这些结果提供了令人信服的证据，表明 Wnt/β-catenin 途径与神经胶质瘤的进展密切相关，可能是该肿瘤的一种新的预后标志物。
