Chromobox Homolog 4 Is Correlated with Prognosis and Tumor Cell Growth in Hepatocellular Carcinoma

• Published in: Annals of surgical oncology 2013-12, Vol.20 (Suppl 3), p.684-692
• Main Authors: Wang, Boqing, Tang, Jianjun, Liao, Dan, Wang, Gang, Zhang, Meifang, Sang, Yi, Cao, Jingying, Wu, Yuanzhong, Zhang, Ruhua, Li, Shengping, Ding, Wei, Zhang, Guoqing, Kang, Tiebang
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell growth; Cell Proliferation; Chromatin remodeling; Cytoplasm; Female; Follow-Up Studies; Gene regulation; Hepatocellular carcinoma; Humans; Immunoenzyme Techniques; Immunohistochemistry; Ligases; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Middle Aged; Neoplasm Staging; Oncology; Polycomb group proteins; Polycomb-Group Proteins - antagonists & inhibitors; Polycomb-Group Proteins - genetics; Polycomb-Group Proteins - metabolism; Prognosis; Proliferating cell nuclear antigen; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Surgery; Surgical Oncology; Survival Rate; Thyroid cancer; Transcription; Translational Research and Biomarkers; Tumor Cells, Cultured; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; α-Fetoprotein
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-013-3171-7

Background Chromobox homolog 4 (CBX4) is a member of the chromobox family of Polycomb group proteins involved in the chromatin remodeling and transcriptional regulation. However, its clinical relevance in hepatocellular carcinoma (HCC) has not yet been explored. Methods Immunohistochemistry was used to analyze cytoplasmic expression of CBX4 in 246 HCC specimens. The expression of CBX4 in HCC cell lines and LO2 was detected by Western blot test. Cell cycle and MTT assays were used to determine the changes of cell growth capacity. The expression of downstream genes related to proliferation was detected by Western blot test. Results The expression of CBX4 was up-regulated in multiple HCC cell lines and clinical samples. Although the CBX4 protein was detectable in both nucleus and cytoplasm in HCC tumor tissues, the high expression of CBX4 in cytoplasm was correlated with the α-fetoprotein level in serum ( P  = 0.036), tumor size ( P  = 0.029), pathologic differentiation ( P  = 0.033), and tumor, node, metastasis classification system stages ( P  = 0.032). Moreover, HCC patients who had a high level of CBX4 in cytoplasm had a shorter overall survival ( P  = 0.003) and recurrence-free survival ( P  = 0.012). Indeed, using HCC cell line, knockdown of CBX4 led to down-regulating proliferating cell nuclear antigen and cyclin E2 as well as up-regulating p16, followed by decreased cell proliferation and impaired cell cycle progression. Conclusions The cytoplasmic CBX4 protein may be a useful prognostic biomarker and a potential therapeutic target for HCC.