title: Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis.
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. Kaplan-Meier 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.forename: Huijuan
authors.initials: H
authors.lastname: Qiu
authors.forename: Muyan
authors.initials: M
authors.lastname: Cai
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Pan
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.forename: Jingping
authors.initials: J
authors.lastname: Yun
authors.forename: Chris Zhiyi
authors.initials: CZ
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D016213:Cyclins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C503669:CCNF protein, human; D016213:Cyclins