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The Expression and Prognosis of FOXO3a and Skp2 in Human Hepatocellular Carcinoma

  • Original Paper
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Pathology & Oncology Research

Abstract

The forkhead box proteins (FOXO proteins) comprise a large family of functionally diverse transcription factors involved in cellular proliferation, transformation, differentiation and longevity. Recently, ubiquitination and proteasome degradation of FOXO3a have been reported. In this study, we investigated the role of FOXO3a and Skp2 in human hepatocellular carcinoma progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 91 specimens. Furthermore in vitro, western-blot analysis and protein stabilization studies were used to study the relationship between FOXO3a and Skp2. We found that the expression of FOXO3a was negatively related with Skp2 expression (r = −0.583; p < 0.05) and FOXO3a expression correlated significantly with histological grade (p = 0.000), cirrhosis (p = 0.015), and tumor size (p = 0.043) while Skp2 expression correlated significantly with histological grade (p = 0.000) and tumor size (p = 0.005). Kaplan-Meier analysis revealed that survival curves of low versus high expressers of FOXO3a and Skp2 showed a highly significant separation in HCC (p < 0.01). Our results suggested that FOXO3a and Skp2 may be considered to be important prognosis in human hepatocellular carcinoma. In vitro studies suggested that the degradation of FOXO3a may dependent on the expression of Skp2 in the proliferated Huh7 cells.

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Acknowledgments

This work was supported by the National Natural Scientific Foundation of China Grant (No.30300099 and No.30770488), Natural Scientific Foundation of Jiangsu Province Grant (No. BK2003035 and No. BK2006547), College and University Natural Scientific Research Programme of Jiangsu Province (No. 03KJB180109 and No. 04KJB320114), Technology Guidance Plan for Social Development of Jiangsu Province Grant (BS2004526), Health Project of Jiangsu Province (H200632), “Liu-Da-Ren-Cai-Gao-Feng” Financial Assistance of Jiangsu Province Grant (No. 2).

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Authors and Affiliations

  1. Department of pathology, affiliated cancer hospital of Nantong University, medical college of Nantong University, Nantong, 226001, China

    Mudan Lu, Chun Cheng, You Wang, Yueming Zhao, Qing Ke, Haiou Liu, Yonghua Liu & Song He

  2. Wuxi Maternal and Child Health Hospital, Wuxi, 214002, China

    Mudan Lu, Wenqun Xue & You Wang

  3. Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 19 Qi-xiu Road, Nantong, Jiangsu, 226001, China

    Aiguo Shen

  4. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, China

    Jianbo Ma, Peng Li & Xiaopeng Cui

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  1. Mudan Lu
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  2. Jianbo Ma
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  3. Wenqun Xue
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  4. Chun Cheng
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  5. You Wang
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  7. Qing Ke
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  8. Haiou Liu
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  9. Yonghua Liu
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  10. Peng Li
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  11. Xiaopeng Cui
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  12. Song He
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  13. Aiguo Shen
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Correspondence to Aiguo Shen.

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Mudan Lu, Jianbo Ma and Wenqun Xue have contributed equally to this work.

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Lu, M., Ma, J., Xue, W. et al. The Expression and Prognosis of FOXO3a and Skp2 in Human Hepatocellular Carcinoma. Pathol. Oncol. Res. 15, 679–687 (2009). https://doi.org/10.1007/s12253-009-9171-z

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  • DOI: https://doi.org/10.1007/s12253-009-9171-z

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