Wu San-Yun, Yu Ming-Xia, Li Xiao-Gai, Xu Shu-Fang, Shen Ji, Sun Zhen, Zhou Xin, Chen Xing-Zhen, Tu Jian-Cheng
Department of Clinical Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China E-mail :
Asian Pac J Cancer Prev. 2014;15(7):3299-304. doi: 10.7314/apjcp.2014.15.7.3299.
The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC).
The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance.
Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63- 21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC.
Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.
本研究旨在分析荷马1(Homer1)是否为肝内胆管癌(ICC)的潜在预后标志物。
采用免疫组织化学法检测ICC组织中Homer1的表达,并通过蛋白质免疫印迹法评估ICC及癌旁组织中的蛋白水平。采用Kaplan-Meier法进行生存分析以评估预后意义。
86例ICC样本中67.4%(58/86)的Homer1表达较高,ICC与癌旁非肿瘤组织之间存在显著差异(p<0.001);高表达与组织学分化差(p=0.019)、TNM分期(p=0.014)、淋巴结转移(p=0.040)及淋巴管浸润(p=0.025)相关。Kaplan-Meier分析显示,Homer1低表达与高表达者的生存曲线比较,总生存期(OS,p=0.001)和无病生存期(DFS,p=0.006)存在高度显著差异,表明Homer1高表达与较差的预后相关。多因素分析显示,Homer1表达是预测ICC患者总生存期[风险比(HR),7.52;95%置信区间(CI),2.63 - 21.47;p=0.002]和无病生存期(HR,11.56;95%CI,5.17 - 25.96;p<0.001)的独立危险因素。
Homer1促进淋巴管浸润,并与ICC的淋巴结转移及不良预后相关。本研究表明,Homer1可能是根治性切除术后ICC患者的独立预后因素,为高危患者的筛查/治疗提供了重要依据。