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Decreased Cezanne expression is associated with the progression and poor prognosis in hepatocellular carcinoma
Jia-hong Wang1, Wei Wei2, Zhi-xing Guo3
1Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. wangjh@sysucc.org.cn.
Background:
Deubiquitinases, such as CYLD, A20 and Cezanne, have emerged as negative regulators that balance the strength and duration of NF-κB signaling through feedback mechanisms. However, how these serial feedback loops are simultaneously disrupted in cancer remains unclear. The purpose of this study is to investigate the correlation of Cezanne expression with clinicopathological/prognostic value in hepatocellular carcinoma (HCC).
Methods:
The expression levels of Cezanne and matrix metallopeptidase 9 (MMP-9) were assessed by immunohistochemistry in 230 HCC specimens. The correlation between expression of Cezanne and MMP-9, clinicopathological/prognostic value in hepatocellular carcinoma was examined.
Results:
Cezanne reduction in HCC was significantly associated with larger tumor, satellite nodule, vascular invasion, TNM stage, BCLC stage and early recurrence. Kaplan-Meier analysis showed that Cezanne was a great predictive factor for overall survival (OS) and time to recurrence (TTR). The expression of Cezanne was decreased in TNM and BCLC stage-dependent manner. In addition, Cezanne reduction was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM stage and BCLC stage. Moreover, Cezanne was negatively associated with MMP-9 among 230 HCC samples. Patients who had Cezanne downregulation, in which cancer cells showed high invasiveness, had shorter TTR and poor OS. Furthermore, the coindex of Cezanne and preoperative serum AFP levels was significantly correlated with OS and TTR.
Conclusion:
Cezanne has a pivotal role in tumor progression and prognosis, and may act as a potential prognostic biomarker for survival in HCC patients.
Insights
Reduced Cezanne expression in hepatocellular carcinoma (HCC) correlates with advanced disease and poor prognosis. Cezanne may serve as a valuable prognostic biomarker for HCC patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling
Background:
- Deubiquitinases (DUBs) like Cezanne regulate NF-κB signaling via feedback loops.
- Disruption of these feedback mechanisms in cancer is not fully understood.
Purpose of the Study:
- Investigate the correlation between Cezanne expression and clinicopathological features and prognosis in hepatocellular carcinoma (HCC).
Main Methods:
- Immunohistochemistry assessed Cezanne and MMP-9 expression in 230 HCC specimens.
- Correlations with clinicopathological data and prognosis were analyzed.
Main Results:
- Cezanne downregulation in HCC associated with larger tumors, vascular invasion, advanced TNM/BCLC stages, and early recurrence.
- Cezanne expression predicted overall survival (OS) and time to recurrence (TTR).
- Cezanne negatively correlated with MMP-9, indicating higher invasiveness in Cezanne-low HCC.
Conclusions:
- Cezanne plays a critical role in HCC tumor progression.
- Cezanne downregulation is linked to poor prognosis and shorter survival in HCC patients.
- Cezanne shows potential as a prognostic biomarker for HCC survival.
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