Role of CCAT/enhancer binding protein (C/EBP) α and C/EBP β in carcinogenesis. of hepatoblastoma and differentiation of hepatoblast.

背景与目的：肝母细胞瘤（Hepatoblastoma，HB）是由肝细胞向肝母细胞分化停滞而发生的肿瘤.我们分析了CCAAT/增强剂结合蛋白（C/EBP）α和C/EBPβ的表达，它们促进肝细胞分化，抑制肝细胞增殖。方法：采用实时荧光定量PCR方法，比较C/EBPα和C/EBPβ在肿瘤和非肿瘤组织中的表达。Ath免疫组化染色分析其表达。将C/EBPα和C/EBPβ的表达水平与临床病理资料进行比较。结果如下：免疫组化结果显示，肿瘤组织中C/EBPα表达较非肿瘤组织上调2.23倍（P=0.013），C/EBPβ表达下调27%（P=0.002）。免疫组化结果显示，同一HB肿瘤低分化部位C/EBP α表达较高分化部位高，C/EBPβ表达较低分化部位低。C/EBPα表达高于各中位数（P=0.05）和C/EBPβ表达低于各中位数（P=0.025）的患者预后较差。采用比例考克斯风险模型，C/EBPα、C/EBPβ高表达和低分化型的风险比分别为3.57（95%可信区间，0.91-14.0，P=0.068）、0.20（0.04-0.96，P=0.044）和13.5（1.70 ~ 107，P=0.014）。结论：分析CIEBPα和C/EBPβ的表达可能有助于HB患者的准确诊断和预后预测。CIEBPα可能不具有抑癌作用，而C/EBPβ具有抑癌作用。由于C/EBPα和C/EBPβ均能促进肝细胞分化，因此C/EBPβ下调可导致分化停滞和细胞增殖，而C/EBPα上调可弥补C/EBPβ在肝细胞分化中的作用。

Background & Aims : Hepatoblastoma (HB) occurs from differentiation arrest of hepatocyte at hepatoblast. We analyzed the expression of CCAAT/enahncer binding protein (C/EBP)α and C/EBPβ that promote hepatocyte differentiation and inhibit proliferation of hepatocytes. Methods : Real-time quantitative PCR was performed to compare the expression of C/EBPα and C/EBPβ between tumor and non-tumor. Their expression was also analyzed Ath immunostaining. The expression levels of C/EBPα and C/EBPβ, were compared with clinoco-pathological data. Results : C/EBPα was up-regulated 2.23 times (P=0.013) and C/EBPβ was down-regulated 27% (P=0.002) in tumor as compared with non-tumor, as confirmed with immunostaining. C/EBPα was more up-regulated and C/EBPβ more down-regulated in poor differentiated part than well differentiated one in the same HB tumor immunohistochemically. Patients with higher expression of C/EBPα (P=0.05), and lower expression of C/EBPβ (P=0.025) than each median showed poor prognosis, respectively. With proportional Cox hazard model, hazard ratio of higher expression of C/EBPα, C/EBPβ, and poorly differentiated type were 3.57 (95% confidential interval, 0.91-14.0, P=0.068), 0.20 (0.04-0.96, P=0.044), and 13.5 (1.70-107, P=0.014), respectively. Conclusion : The analysis of expression of CIEBPα and C/EBPβ may be useful for precise diagnosis and prediction of prognosis of HB patients. CIEBPα may not act as a tumor suppressor in HB while C/EBPβ does. Since both C/EBPα and C/EBPβ promote hepatocyte differentiation, down-regulation of C/EBPβ led to the differentiation arrest and cell proliferation, and C/EBPα was up-regulated to compensate the role of C/EBPβ in hepatocyte differentiaion.