Open AccessLow cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis
Author(s) -
Fu Jia,
Qiu Huijuan,
Cai Muyan,
Pan Yinghua,
Cao Yun,
Liu Lili,
Yun Jingping,
Zhang Chris Zhiyi
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12100
Subject(s) - cyclin , cyclin e , cyclin e1 , cancer research , cyclin a , cyclin d1 , cyclin d , biology , immunohistochemistry , hepatocellular carcinoma , cyclin b1 , cell cycle , cyclin b , cancer , pathology , medicine , immunology , cyclin dependent kinase 1 , genetics
Cyclin F , capable of forming S kp1‐ C ul1‐ 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 . K aplan – M eier 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.