Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations.
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.
Liu
Ce
C
Department of Neurosurgery, The 309th Hospital of PLA, Beijing, People's Republic of China.
Tu
Yanyang
Y
Sun
Xiaoyang
X
Jiang
Jian
J
Jin
Xiaodong
X
Bo
Xiangfei
X
Li
Zhengming
Z
Bian
Aimiao
A
Wang
Xiaodong
X
Liu
Dai
D
Wang
Zhengmei
Z
Ding
Lianshu
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D019938:Cyclin D1 / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D051155:Wnt1 Protein / Q000096:biosynthesis*; D051176:beta Catenin / Q000096:biosynthesis*
C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin; D019938:Cyclin D1
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