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Expression of Hedgehog Pathway Components is Associated with Bladder Cancer Progression and Clinical Outcome

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Pathology & Oncology Research

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.

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Acknowledgments

This work was supported by grants from the Natural Science Foundation of Guangdong Province (04003650), National Natural Science Foundation of China (30872960), Key projects of Bureau of Health in Guangzhou Municipality (201102A212015) and projects of Guangdong Key Laboratory of Urology (2010A060801016).

Competing interests

There are none competing interests in this study.

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Authors and Affiliations

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

    Hui-chan He, Jia-hong Chen, Xi-bin Chen, Chao Cai, Yu-xiang Liang, Zhao-dong Han, Qi-shan Dai, Yan-ru Chen, Fu-neng Jiang & Wei-de Zhong

  2. Urology Key Laboratory of Guangdong Province, First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou, 510230, China

    Guo-hua Zeng & Wei-de Zhong

  3. Department of Urology, Guizhou Provincial People’s Hospital, Guizhou, 550002, China

    Jian-guo Zhu

  4. Southern Medical University, Guangzhou, 510515, China

    Guo-qiang Qin & Jian-guo Zhu

  5. Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China

    Wei-de Zhong

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  1. Hui-chan He
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  2. Jia-hong Chen
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  10. Guo-hua Zeng
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  12. Fu-neng Jiang
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  13. Wei-de Zhong
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Corresponding author

Correspondence to Wei-de Zhong.

Additional information

Hui-chan He, Jia-hong Chen and Xi-bin Chen offered equal contributions to this study.

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He, Hc., Chen, Jh., Chen, Xb. et al. Expression of Hedgehog Pathway Components is Associated with Bladder Cancer Progression and Clinical Outcome. Pathol. Oncol. Res. 18, 349–355 (2012). https://doi.org/10.1007/s12253-011-9451-2

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  • DOI: https://doi.org/10.1007/s12253-011-9451-2

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