High expression of AP-4 predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy.
The aim of this study was to evaluate the association between activating enhancer binding protein 4 (AP-4) tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The levels of AP-4 mRNA and protein in tumor and para-tumor tissue were evaluated in 30 HCC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Additionally, AP-4 protein expression in 112 HCC was analyzed by immunohistochemistry. The correlation of AP-4 expression and patients' clinicopathological parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. By RT-PCR and Western blot, the levels of AP-4 mRNA and protein were significantly higher in HCC, compared to that in para-tumor tissue (p < 0.001). Immunohistochemical staining revealed that AP-4 was highly expressed in 53.6 % of the HCC patients. The AP-4 expression level was closely associated with serum alpha fetoprotein elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that a high expression level of AP-4 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that AP-4 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high expression level of AP-4 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that AP-4 may be a potential target of antiangiogenic therapy for HCC.
Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Ben-Shun
BS
Hu
Gang
G
Zhao
Hai-Feng
HF
Yu
Ke
K
Chen
Jia-Hong
JH
Dong
Jing-Wang
JW
Tan
D033964:Adaptor Protein Complex 4 / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000032:analysis
D033964:Adaptor Protein Complex 4; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000509:alpha-Fetoproteins