Prognostic significance of Cbx4 expression and its beneficial effect for transarterial chemoembolization in hepatocellular carcinoma

Abstract

Our recent investigations showed that polycomb chromobox 4 (Cbx4) promotes angiogenesis and metastasis of hepatocellular carcinoma (HCC) through its sumoylating action on hypoxia-inducible factor-1α protein. Here, we attempt to identify the prognostic significances of Cbx4 by a retrospective analyses in 727 cases of HCC patients with and without postoperative transarterial chemoembolization (TACE) or transarterial embolization (TAE). Binary logistic regression tests indicated that Cbx4 is correlated with histological grading, tumor-node-metastasis stage, microvessel density, distant metastasis and hematogenous metastasis of HCC. By univariate and multivariate analyses, we show that Cbx4 is an independent prognostic factor of HCC, and both TAE and TACE treatments have no effects on the overall survival in HCC patients with low Cbx4 expression. More intriguingly, TACE prolongs, while TAE shortens, the overall survival of HCC patients with high Cbx4 expression, indicating that Cbx4 is a good biomarker on decision-making to perform postoperative TACE in HCC patients. Moreover, Cbx4 overexpression enhances while Cbx4 silencing antagonizes doxorubicin-induced cell death of HCC cell lines. In conclusion, Cbx4 is an independent prognostic factor for HCC patients, and the patients with high Cbx4 expression should receive postoperative TACE treatment to improve their survival.

SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma

“…Analysis of a large cohort of HCC tissues reported that Cbx4 is highly expressed and positively correlated with poor overall survival of HCC patients (37,38). Interestingly, Cbx4 is the sole Cbx family members that induces angiogenesis promoting the expression of hypoxia-induced vascular endothelial growth factor (VEGF) in HCC cells via induced-HIF-1α SUMOylation.…”

RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways

“…Hepatocellular carcinoma (HCC) is the major histological subtype of liver cancer. Because of its high mortality, HCC has been regarded as the leading cause of cancer deaths worldwide [3, 4]. The traditional treatments for HCC include local ablation, surgical resection, chemotherapy, and liver transplantation.…”

Micro RNA‐4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy

“…However, many studies have suggested that pa‐TACE displays different therapeutic effects on hepatocellular carcinoma with different genetic profiles. For example, different genetic features such as different expression of polycomb chromobox 4 and x‐ray repair complementing 4 among individuals with hepatocellular carcinoma have been proven to modify MVD, and ultimately lead to unsuccessful pa‐TACE treatment . Genetic changes in a disintegrin and metalloproteinase with thrombospondin motifs 5, microRNA‐1268a, microRNA‐196a, and microRNA‐499a may change individual's response to pa‐TACE treatment and result in treatment failure …”

“…The cellular sensitivity on antitumor drugs was determined using our previously published half‐maximal inhibitory concentration (IC50) method . Briefly, SMMC‐7721 cells were transfected with mature microRNA‐4651 mimics, its inhibitor, or null control (GenePharma, Shanghai, China) using Lipofectamine 2000 (ca#11668‐027, Invitrogen).…”

“…The cellular sensitivity on antitumor drugs was determined using our previously published half-maximal inhibitory concentration (IC50) method. (32) Briefly, SMMC-7721 cells were transfected with mature microRNA-4651 mimics, its inhibitor, or null control (GenePharma, Shanghai, China) using Lipofectamine 2000 (ca#11668-027, Invitrogen). In the present study, transfection efficiency was elucidated using the LV200 system and according to the following valid criteria: the number of positive transfected cells being more than 40% of total cells.…”