• Open Access

Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis

Authors

  • Jia Fu,

    1. State Key Laboratory of Oncology in South China, Guangzhou, China
    2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Huijuan Qiu,

    1. Department of Traditional Chinese Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Muyan Cai,

    1. State Key Laboratory of Oncology in South China, Guangzhou, China
    2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Yinghua Pan,

    1. Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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  • Yun Cao,

    1. State Key Laboratory of Oncology in South China, Guangzhou, China
    2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Lili Liu,

    1. State Key Laboratory of Oncology in South China, Guangzhou, China
    2. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Jingping Yun,

    Corresponding author
    1. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
    • State Key Laboratory of Oncology in South China, Guangzhou, China
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  • Chris Zhiyi Zhang

    Corresponding author
    1. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
    • State Key Laboratory of Oncology in South China, Guangzhou, China
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To whom correspondence should be addressed.

E-mails: yunjp@sysucc.org.cn; ls01zzy@hotmail.com

Abstract

Cyclin F, capable of forming Skp1-Cul1-F-box protein ubiquitin ligase complex, is implicated in controlling centrosome duplication and preventing genome instability. Cyclin F oscillates during cell cycle with a similar pattern to cyclin A. However, its expression and significance in cancer remain obscure. In this study, we showed that cyclin F was noticeably decreased in 16 pairs of tissue samples of hepatocellular carcinoma (HCC) compared to paracarcinoma tissues, at both mRNA and protein levels. Immunohistochemical staining data revealed that in 71.8% (176/245) of HCC cases, cyclin F expression in tumor tissue was much lower than that in nontumorous tissue. Low cyclin F expression, defined by receiver operating characteristic curve analysis, was present in 69.0% of HCC patients. Low expression of cyclin F was significantly correlated with tumor size, clinical stage, serum alpha-fetoprotein level and tumor multiplicity. Further study showed that cyclin F expression was reversely associated with tumor differentiation in HCC. KaplanMeier analysis indicated that low cyclin F expression was related to poor overall survival and recurrence-free survival. The prognostic impact of cyclin F was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low cyclin F expression was an independent poor prognostic marker for overall survival. We conclude that cyclin F is downregulated in HCC and is a promising prognostic marker for patients suffering from this deadly disease.

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