title: Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The 309th Hospital of PLA, Beijing, People's Republic of China.
authors.forename: Ce
authors.initials: C
authors.lastname: Liu
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Tu
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jin
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Bo
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Li
authors.forename: Aimiao
authors.initials: A
authors.lastname: Bian
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Dai
authors.initials: D
authors.lastname: Liu
authors.forename: Zhengmei
authors.initials: Z
authors.lastname: Wang
authors.forename: Lianshu
authors.initials: L
authors.lastname: Ding
mesh_terms: 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*
chemical_list: C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051155:Wnt1 Protein; D051176:beta Catenin; D019938:Cyclin D1
references.citation: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Nov;25(11):1010-2
references.pmid: 19900369
references.citation: World J Surg Oncol. 2007 Feb 19;5:21
references.pmid: 17309796
references.citation: Eur J Cancer. 2008 Nov;44(17):2680-8
references.pmid: 18790633
references.citation: BMC Cancer. 2009 Jun 26;9:206
references.pmid: 19558675
references.citation: J Cell Biol. 2002 Apr 29;157(3):429-40
references.pmid: 11980918
references.citation: Cancer Gene Ther. 2009 Apr;16(4):351-61
references.pmid: 18949017
references.citation: Cancer. 2004 Sep 15;101(6):1345-56
references.pmid: 15316903
references.citation: Oncogene. 2008 Feb 28;27(10):1478-88
references.pmid: 17724465
references.citation: Clin Neuropathol. 2009 Sep-Oct;28(5):362-72
references.pmid: 19788052
references.citation: Oncol Rep. 2006 Sep;16(3):505-11
references.pmid: 16865250
references.citation: Am J Pathol. 2002 Oct;161(4):1315-23
references.pmid: 12368205
references.citation: Thyroid. 2004 Dec;14(12):1020-9
references.pmid: 15650354
references.citation: J Pathol. 2006 Jan;208(1):91-9
references.pmid: 16278819
references.citation: Br J Cancer. 2004 Jan 12;90(1):224-9
references.pmid: 14710233
references.citation: Cancer Res. 2002 Jan 1;62(1):277-82
references.pmid: 11782388
references.citation: Neurochem Int. 2009 Sep;55(5):307-17
references.pmid: 19576519
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4262-6
references.pmid: 10759547
references.citation: EMBO J. 1998 Mar 2;17(5):1371-84
references.pmid: 9482734
references.citation: Oncol Rep. 2005 Dec;14(6):1437-43
references.pmid: 16273236
references.citation: Clin Cancer Res. 2009 Nov 1;15(21):6683-93
references.pmid: 19861461
references.citation: Oncol Rep. 2005 Jun;13(6):1095-9
references.pmid: 15870927
references.citation: Am J Pathol. 2002 Nov;161(5):1619-34
references.pmid: 12414510
references.citation: Med Oncol. 2011 Jun;28(2):608-14
references.pmid: 20300972
references.citation: Genes Dev. 2000 Aug 1;14(15):1837-51
references.pmid: 10921899
references.citation: J Cancer Res Clin Oncol. 2003 Apr;129(4):199-221
references.pmid: 12707770
references.citation: Science. 2002 May 31;296(5573):1644-6
references.pmid: 12040179