CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma
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Hao Zheng1,*, Wei-hua Jiang2,*, Tao Tian1,*, Hai-song Tan3,*, Ying Chen2, Guang-lei Qiao2, Jun Han1, Sheng-yu Huang6, Yuan Yang1, Shuai Li4, Zhen-guang Wang1, Rong Gao5, Hao Ren5, Hao Xing1, Jun-sheng Ni1, Lin-Hui Wang3, Li-jun Ma2, Wei-ping Zhou1
1The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China
2Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China
3Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
4Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY, 12180, United States of America
5Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China
6The Fourth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China
*These authors have contributed equally to this work
Wei-ping Zhou, email: [email protected]
Li-jun Ma, email: [email protected]
Lin-Hui Wang, email: [email protected]
Keywords: CBX6, S100A9, hepatocellular carcinoma, proliferation, biomarker
Received: December 06, 2016 Accepted: January 09, 2017 Published: January 20, 2017
Aberrant chromobox (CBX) family protein expression has been reported in a variety of human malignancies. However, the role of CBX6 in hepatocellular carcinoma (HCC) progression and patient prognosis remains unknown. In this study, we found that CBX6 was frequently up-regulated in HCC clinical samples and HCC cell lines and that CBX6 expression was significantly correlated with larger tumor sizes (≥ 5 cm, p = 0.011) and multiple tumors (n ≥ 2, p = 0.018). Survival analyses indicated that patients with higher CBX6 expression levels had significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with lower CBX6 expression levels, and multivariate analyses confirmed that increased CBX6 expression was an independent unfavorable prognostic factor for HCC patients. Functional study demonstrated that CBX6 profoundly promoted HCC cell growth both in vitro and in vivo, and mechanistic investigation revealed that the S100A9/NF-κB/MAPK pathway was essential for mediating CBX6 function. In conclusion, our results represent the first evidence that CBX6 contributes to tumor progression and indicate that the protein may serve as a novel prognostic biomarker for HCC and as a therapeutic target in the treatment of the disease.
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