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hedgehog 通路成分的表达与膀胱癌的进展和临床结局相关。

Expression of hedgehog pathway components is associated with bladder cancer progression and clinical outcome.

机构信息

Department of Urology, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, 510180, China.

出版信息

Pathol Oncol Res. 2012 Apr;18(2):349-55. doi: 10.1007/s12253-011-9451-2. Epub 2011 Aug 24.


DOI:10.1007/s12253-011-9451-2
PMID:21861243
Abstract

Hedgehog (Hh) pathway has been implicated in the tumorigenesis of a large number of human tumors. But its effects on the progression and prognosis of bladder cancer remain poorly understood. The aim of this study was to investigate expression patterns of Hh pathway components in bladder cancer and to elucidate their prognostic values in this tumor. The expression of sonic hedgehog (Shh), its receptor Patched (Ptch1), and downstream transcription factor Gli1 in 118 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between the expression of these three proteins and clinicopathologic features and prognosis. Immunohistochemical staining results showed the localizations of Shh and Ptch1 proteins to be mainly located in the cytoplasm of bladder cancer cells, whereas Gli1 was mainly localized in the nuclear of tumor cells. Additionally, positive expression of Shh, Ptch1 and Gli1 proteins was correlated with pathological stage (P = 0.006, 0.006 and 0.008, respectively), venous invasion (P = 0.01, 0.01 and 0.012, respectively) and lymph node metastasis (P = 0.009, 0.01 and 0.013, respectively), but not with other factors including age, gender, tumor grade and recurrence of superficial cancer. Moreover, patients with positive expression of Shh, Ptch1 and Gli1 proteins respectively showed poorer disease-free (P = 0.002, 0.002 and 0.001, respectively) and overall survival (all P < 0.001) than those with negative expression of these three proteins. Univariate and multivariate analysis of prognostic factors in bladder cancer patients indicated that the expression patterns of Shh, Ptch1 and Gli1 proteins were independent unfavorable prognostic factors (all P < 0.001). This is the first report describing about the correlation between Hh pathway and the prognosis of bladder cancer. Expression of Shh, Ptch1 and Gli1 proteins was greater in bladder cancers than in the adjacent normal tissues. The examination of their expression is potentially valuable in prognostic evaluation of bladder cancer.

摘要

Hedgehog (Hh) 途径已被牵连到许多人类肿瘤的肿瘤发生中。但其对膀胱癌进展和预后的影响仍知之甚少。本研究旨在研究膀胱癌中 Hh 途径成分的表达模式,并阐明其在该肿瘤中的预后价值。通过免疫组织化学法检测 118 例膀胱癌标本和 30 例相邻正常膀胱组织中 sonic hedgehog (Shh)、其受体 patched (Ptch1) 和下游转录因子 Gli1 的表达。应用统计学分析来检验这三种蛋白的表达与临床病理特征和预后之间的关系。免疫组织化学染色结果显示,Shh 和 Ptch1 蛋白的定位主要位于膀胱癌细胞质中,而 Gli1 主要定位于肿瘤细胞核中。此外,Shh、Ptch1 和 Gli1 蛋白的阳性表达与病理分期(P=0.006、0.006 和 0.008)、静脉侵犯(P=0.01、0.01 和 0.012)和淋巴结转移(P=0.009、0.01 和 0.013)相关,但与其他因素如年龄、性别、肿瘤分级和表浅癌复发无关。此外,Shh、Ptch1 和 Gli1 蛋白阳性表达的患者无病生存率(P=0.002、0.002 和 0.001)和总生存率(均 P<0.001)均较阴性表达者差。膀胱癌患者预后因素的单因素和多因素分析表明,Shh、Ptch1 和 Gli1 蛋白的表达模式是独立的不良预后因素(均 P<0.001)。这是首次描述 Hh 途径与膀胱癌预后的相关性。Shh、Ptch1 和 Gli1 蛋白在膀胱癌中的表达高于相邻正常组织。检测其表达可能对膀胱癌的预后评估有价值。

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本文引用的文献

[1]
GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor.

Biochem Biophys Res Commun. 2010-12-21

[2]
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Prog Mol Biol Transl Sci. 2010

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Cancer. 2010-10-19

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Genetic variations in the sonic hedgehog pathway affect clinical outcomes in non-muscle-invasive bladder cancer.

Cancer Prev Res (Phila). 2010-9-21

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Acta Histochem. 2010-7-2

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Activation of the Hedgehog pathway in pilocytic astrocytomas.

Neuro Oncol. 2010-3-11

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Overexpression of smoothened activates the sonic hedgehog signaling pathway in pancreatic cancer-associated fibroblasts.

Clin Cancer Res. 2010-3-9

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Increased expression of the hedgehog signaling pathway in pediatric solid malignancies.

J Pediatr Surg. 2010-2

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