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.

Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

“…We therefore propose that the transcriptional suppression mediated by cyclin F serves as an important temporal safeguard maintaining repression of target genes until the p53 response eventually contributes through mechanisms such as the p53-p21-DREAM-CDE/CHR pathway 34,35 . Very interestingly, cyclin F has been shown to be reduced in certain cancer types 36 , whereas B-Myb is overexpressed in several types of cancers 37 . It has been reported that low cyclin F levels correlate with poor differentiation and unfavourable prognosis in hepatocellular carcinoma 36 .…”

“…Very interestingly, cyclin F has been shown to be reduced in certain cancer types 36 , whereas B-Myb is overexpressed in several types of cancers 37 . It has been reported that low cyclin F levels correlate with poor differentiation and unfavourable prognosis in hepatocellular carcinoma 36 . It is therefore possible that cyclin F plays a relevant role in cancer development by preventing unscheduled cell proliferation and genomic instability through the suppression of B-Myb.…”

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

“…Moreover, an ideal biomarker should be easily accessible and quantifiable, and procedures for measuring a biomarker should be minimally invasive, inexpensive, accurate, and acceptable to both the patient and the physician. While a variety of proteins and other characteristics associated with a type of cancer including DNA methylation, circulating tumor cells, and histone modifications, have attracted the attention of researchers for early diagnosis and prognosis of HCC, the availability of clinically applicable biomarkers remains limited (Liu et al, 2012;Shen et al, 2012;Fu et al, 2013;Ji et al, 2014).…”

Roles of F-box proteins in cancer

“…However, the depletion of Fbxo1 in mouse embryonic fibroblasts (MEFs) caused cell cycle defects by an unclear mechanism 59 . Notably, FBXO1 is downregulated in hepatocellular carcinoma, and low expression levels of FBXO1 are associated with larger tumour size, advanced clinical stage, tumour multiplicity and poorer survival, which suggests that FBXO1 could be a promising prognostic marker for hepatocellular carcinoma 60 .…”