摘要目的 探讨Omi/HtrA2的表达水平在预测肝细胞癌预后中的作用及其与缺氧诱导因子(HIF)-1α的相关性.方法 采用免疫组化法检测43例原发肝癌组织标本中Omi/HtrA2和HIF-1α的表达水平,并结合随访资料进行分析.将重组质粒pTRE-HIF-1α转染到HepG2Tet-on细胞,以含0、0.02、0.20、1.00、2.00、5.00 mg/L浓度强力霉素的培养液体外培养已转染pTRE-HIF-1α的HepG2Tet-on细胞,应用RT-PCR法检测不同表达水平HIF-1α对Omi/HtrA2表达的影响.结果 Omi/HtrA2表达与肝细胞癌肝门淋巴结转移和术后2年内肝内复发相关.Omi/HtrA2表达阳性患者肝癌切除术后1、2、3、4、5年累积生存率明显高于Omi/HtrA2表达阴性患者(x2=6.13,P=0.013).HIF-1α和Omi/HtrA2在免疫组化染色的同一切片中,HIF-1 α表达阴性或者弱阳性标本中Omi/HtrA2多表达为阳性或强阳性,HIF-1α表达阳性或者强阳性标本中Omi/HtrA2多表达为阴性或弱阳性.RT-PCR方法检测结果显示,随着HIF-1α表达水平的增加,Omi/HtrA2基因的表达强度逐渐降低(F=106.766,P＜0.01).结论 Omi/HtrA2可能成为预测肝细胞癌预后的一个重要分子标记.肝癌组织中Omi/HtrA2与HIF -1α表达水平呈负相关,在Omi/HtrA2参与肝癌细胞凋亡过程中,HIF-1α可能参与调控了Omi/HtrA2的表达.

abstractsObjectives To investigate the prognostic significance of Omi/HtrA2 expression,and the correlation between Omi/HtrA2 and Hypoxia-inducible factor (HIF)-1α in primary hepatocelluar carcinoma cells.Methods The expression of HIF-1α and Omi/HtrA2 in 43 cases of hepatic carcinoma tissues were detected immunohistochemically.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.The change of Omi/HtrA2 expression in HepG2 cell was measured after HIF-1α expression of HepG2 in vitro was regulated by Tet-on expression system.Results Omi/HtrA2 expression was correlated with lymph node metastasis and recurring within liver during 2 years.Statistical analysis estimation showed the cumulative survival rate of post-hepatectomy for the patients with the positive expression of Omi/HtrA2 was higher than that for other patients with the negative expression of Omi/HtrA2 (x2 =6.13,P =0.013 ).In the common paraffin-embedded specimen of hepatocellular carcinoma,most of the samples showing negative or weak positive HIF-1α immunopositivity showed moderate positive or strong positive Omi/HtrA2 immunopositivity,while most of the samples showing moderate positive or strong positive HIF-1α immunopositivity showed negative or weak positive Omi/HtrA2 immunopositivity.The mRNA expression intensity of Omi/HtrA2 was decreasing with the HIF-1o expression increasing,and the difference was statistically significant( F =106.766,P ＜ 0.01 ).Conclusions Omi/HtrA2 may be an important prognostic marker for primary hepatocelluar carcinoma.Omi/HtrA2 expression is reversely correlated with HIF-1αexpression in hepatocelluar carcinoma.During the apoptotic process Omi/HtrA2 participating in hepatocelluar carcinoma cells,HIF-1 α is involved in the controlling and regulating of Omi/HtrA2 expression.