预测索拉菲尼治疗晚期原发性肝细胞癌疗效的分子标志物的研究

Candidate molecular markers for predicting sorafenib efficacy in treating advanced hepatocellular carcinoma

目的探寻可能预测索拉菲尼治疗晚期原发性肝细胞癌(hepatocellular carcinoma,HCC)疗效的分子标志物。方法回顾性分析应用索拉菲尼治疗的54例晚期HCC患者临床资料,将索拉菲尼治疗前病理组织切片分别以抗体VEGFR、p ERK、p S6K、PTEN进行免疫组组织化学染色(IHC),根据各抗体染色结果的不同分为高表达组和低表达组,结合索拉菲尼治疗后的疾病进展时间(time to progression,TTP)进行对比分析,得到可能预测索拉菲尼治疗HCC疗效的分子标志物。结果 VEGFR、p ERK高表达组较低表达组的TTP明显延长(P<0.05),PS6K两组之间的TTP无显著差异(P>0.05),PTEN几乎无阳性表达。结论索拉菲尼治疗的肝癌组织中VEGFR、p ERK高表达患者能够获得较长的TTP,VEGFR、p ERK可能作为预测索拉菲尼治疗晚期HCC疗效的分子标志物。

Objective To investigate the candidate molecular markers for predicting the efficacy of sorafenib in treatment of advanced hepatocellular carcinoma（ HCC）. Methods Clinical data of 54 patients with identified advanced HCC and receiving sorafenib treatment who hospitalized in the First Affiliated Hospital of Sun Yat-Sen University from December 2008 to October 2011 were collected and analyzed in this study. Their liver tissue sections from the paraffin-embedded liver tumor biopsies before sorafenib treatment were analyzed with immunohistochemical staining（ IHC） for phosphorylated extracellular signal regulated kinase（ p ERK）,vascular endothelial growth factor receptor（ VEGFR）,p70 S6 kinase（ Ps6k） and phosphatase and tensin homologue deleted on chromosome ten（ PTEN）. According to the results of IHC,the patients were divided into high- and low-expression subgroups,and then analyzed with the time to progression（ TTP） of the cohort in order to investigate the molecular markers for predicting the efficacy of sorafenib. Results The TTP was significantly longer in the patients with higher expression of VEGFR and p ERK than those with lower expression（ P 〈 0. 05）. But there was no difference in the TTP between the patients with high and low expression of Ps6k（ P 〉 0. 05）. No positive expression of PTEN was seen in the cohort. Conclusion In the treatment of advanced HCC,sorafenib will cause longer TTP in the patients with high expression levels of VEGFR and p ERK. VEGFR and p ERK maybe the candidates as molecular markers for sorafenib in treating advanced HCC.