【摘要】 目的探讨骨桥蛋白(OPN)、P53、血管内皮生长因子(VEGF)在乙型肝炎病毒(HBV)相关肝细胞肝癌(肝癌)组织中的表达情况,以及OPN表达与根治性切除(R0)术后短期复发和预后的关系。方法回顾性研究2003年1月至2008年12月在青岛大学医学院附属医院肝胆外科行R0切除术的237例HBV相关肝癌标本。患者男204例,女33例;年龄15~82岁,中位年龄54岁。患者均签署知情同意书,符合医学伦理学规定。另取肿瘤旁1 cm内的癌旁组织81例和肝硬化活组织检查(活检)标本79例作为对照组。应用组织芯片技术和免疫组织化学PV-6000二步法检测HBV相关肝癌组织中OPN、P53、VEGF表达阳性率。采用χ2检验比较肝癌组织的OPN表达与患者临床病理学参数、P53、VEGF的关系;采用Kaplan-Meier法和Log-rank检验法进行生存分析,采用Cox比例风险回归模型进行肿瘤短期复发和生存预后的危险因素分析。结果所有肝癌患者均接受随访,随访时间1~102个月,中位随访时间43个月。术后短期复发55例,其中肝内复发占56%(31/55),肝外转移占44%(24/55);非短期复发89例,其中肝内复发占80%(71/89),肝外转移占20%(18/89)。OPN在肝癌组织、癌旁组织和肝硬化组织中的表达阳性率分别为37%(88/237)、17%(14/81)和14%(11/79),肝癌组织与癌旁组织、肝硬化组织的OPN表达阳性率比较差异有统计学意义(χ2=12.44,16.53;P<0.05)。短期复发患者OPN表达阳性率51%(28/55),非短期复发者35%(31/89),无复发患者OPN表达阳性率31%(29/93),短期复发组OPN表达阳性率明显高于非短期复发组和无复发组(χ2=4.181,5.679;P=0.041、0.017)。肝癌组织P53表达阳性率为26%(61/237),VEGF表达阳性率为77.2%(183/237)。OPN阳性组P53、VEGF表达阳性率均明显高于阴性组,差异有统计学意义(χ2=6.947,4.14;P<0.05)。血清甲胎蛋白(AFP)≥400μg/L、有卫星灶、血管有癌栓、组织学中低分化和TNM分期Ⅲ~Ⅳ期者OPN表达阳性率明显升高(均为P<0.05)。OPN表达阳性组的中位生存期为49.6个月,明显低于阴性组84.0个月;两组生存率比较差异有统计学意义(χ2=5.916,P=0.015)。OPN阳性是HBV相关肝癌患者术后短期复发和生存预后的独立危险因素。结论 HBV相关肝癌组织中OPN阳性表达增高,OPN与P53、VEGF的表达有关系;OPN的阳性表达是HBV相关肝癌患者术后短期复发和生存预后的独立危险因素,肝癌组织OPN阳性表达预示短期复发率高,预后不良。更多还原

【Abstract】 Objective To evaluate the expressions of osteopontin(OPN),P53 and vascular endothelial growth factor(VEGF)in the hepatitis B virus(HBV) related hepatocellular carcinoma(HCC) tissues and the relation between the OPN expression and the short-term recurrence and prognosis of patients after radical liver resection(R0).Methods A total of 237 HBV-related HCC tissue specimens from patients who received R0 hepatectomy in the Department of Hepatobiliary Surgery,Affiliated Hospital of Medical College,Qingdao University from January 2003 to December 2008,were studied retrospectively.There were 204 males and 33 females with the age range from 15 to 82 years old and the median age of 54 years old.The informed consents of all patients were obtained and the ethical committee approval was received.Eighty-one para-carcinoma tissue specimens within 1 cm close to the tumor and 79 biopsy specimens of liver cirrhosis were collected as the control group.The positive expression rate of OPN,P53,VEGF were examined using tissue microarray and PV-6000 two-step methods of immunohistochemistry.The relations between the OPN expression and the HCC patients’ clinic pathological parameters,the P53 expression,as well as VEGF expression were compared by chi-square test.Survival analysis was carried out using Kaplan-Meier survival curve and Log-rank test.The risk factor analysis of tumor short-term recurrence and the prognosis analysis were carried out using Cox proportional hazard model.Results All patients were followed up for 1 ~102 months(the median time 43 months).Short-term recurrence of HCC was observed in 55 patients after R0 hepatectomy with the intrahepatic recurrence rate 56%(31/55) and the extrahepatic metastasis rate 44%(24/55).Among 89 patients without short-term recurrence 80%(71/89) developed intrahepatic recurrence and 20%(18/89) developed extrahepatic metastasis.The positive expression rates of OPN in the HCC tissues,para-cacinoma tissues and liver cirrhosis tissues were 37%(88/237),17%(14/81) and 14%(11/79) respectively.There were significant differences among the OPN positive expression rates in the HCC tissues,para-cacinoma tissues and liver cirrhosis tissues( χ2=12.44,16.53; P<0.05).The positive expression rate of OPN in the patients with short-term HCC recurrence was 51%(28/55),35%(31/89) in the non-short-term HCC recurrence patients,and 31%(29/93) in the recurrence-free patients.The positive expression rate of OPN in the patients with short-term HCC recurrence was evidently higher,compared with that in the non-short-term HCC recurrence and recurrence-free patients( χ2=4.181,5.679; P=0.041,0.017).The positive expression rate of P53 and VEGF in the HCC tissues were 26%(61/237),77.2%(183/237) respectively.The positive expression rate of P53 and VEGF in the OPN positive tissues were both higher than that in the OPN negative tissues.There were significant differences( χ2=6.947,4.14; P<0.05).The median survival time in the positive OPN expression group was 49.6 months,which was shorter than that in the negative group(84.0 months)( χ2=5.916,P=0.015).There was significant difference for the survival rates between 2 groups.The positive expression of OPN is the independent risk factor for short-term recurrence and the prognosis in patients with HBV related HCC after the operation.Conclusions The positive expression rate of OPN is significantly higher in the HBV related HCC tissues.The expression of OPN shows relation with P53 and VEGF expression.The positive expression of OPN is the independent risk factor for short-term recurrence and the prognosis in patients with HBV related HCC after the operation.The positive expression of OPN indicates higher incidence of short-term recurrence and poorer prognosis.更多还原