Chromobox homolog 4 is correlated with prognosis and tumor cell growth in hepatocellular carcinoma.
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.
Department of Hepatopancreatobiliary Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.
Boqing
B
Wang
Jianjun
J
Tang
Dan
D
Liao
Gang
G
Wang
Meifang
M
Zhang
Yi
Y
Sang
Jingying
J
Cao
Yuanzhong
Y
Wu
Ruhua
R
Zhang
Shengping
S
Li
Wei
W
Ding
Guoqing
G
Zhang
Tiebang
T
Kang
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008025:Ligases; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D063146:Polycomb-Group Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D063146:Polycomb-Group Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human