title: CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jiang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Hai-Song
authors.initials: HS
authors.lastname: Tan
authors.affiliation: Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China.
authors.forename: Guang-Lei
authors.initials: GL
authors.lastname: Qiao
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: The Fourth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Huang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY, 12180, United States of America.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhen-Guang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xing
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Ni
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D063146:Polycomb-Group Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D063146:Polycomb-Group Proteins; C000609719:cbx6 protein, human
keywords: CBX6; S100A9; biomarker; hepatocellular carcinoma; proliferation