上皮细胞黏附分子在肝内胆管癌病人中的表达及其与预后和肿瘤复发转移的关系

Expression profile of epithelial cell adhesion molecule in patients with intrahepatic cholangiocarcinoma and its relationship with prognosis, recurrence and metastasis

目的研究上皮细胞黏附分子(epithelial cell adhesion molecule,EpCAM)在肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)病人中的表达情况及其与预后和术后肿瘤复发、淋巴转移的关系。方法回顾性分析2015年1月至2017年12月在北京大学人民医院行手术治疗的42例ICC病人的临床、病理及预后资料,应用免疫组织化学染色测定EpCAM的表达水平,分析其与预后及肿瘤复发转移的关系。采用Pearson检验进行相关性分析,Kaplan-Meier法分析术后生存率,log-rank检验比较组间生存率的差异,采用多因素Cox回归分析生存率的影响因素。结果在42例ICC肿瘤组织中,EpCAM高表达的比例为85.7%(36/42)。其中,EpCAM高表达病人术后肿瘤复发率在90.0%以上,并且EpCAM表达水平与淋巴转移存在明显的相关性(r=0.356,P=0.021)。此外,单因素分析显示:EpCAM高表达与EpCAM低表达的ICC病人比较,3年总生存率(30.6%比83.3%,χ^(2)=4.043,P=0.044)和3年无病生存率(16.7%比66.7%,χ^(2)=4.599,P=0.032)更低,5年总生存率(22.2%比83.3%,χ^(2)=6.355,P=0.012)和5年无病生存率(11.1%比66.7%,χ^(2)=7.006,P=0.008)也更低。多因素分析显示:EpCAM表达水平是ICC病人术后3年无病生存率(P=0.030)、5年总生存率(P=0.041)、5年无病生存率(P=0.019)的独立影响因素;EpCAM高表达的ICC病人术后3年复发风险高于EpCAM低表达病人[HR=4.902,95%CI(1.162,20.679),P=0.030],5年死亡风险[HR=8.069,95%CI(1.094,59.532),P=0.041]和5年复发风险[HR=5.594,95%CI(1.328,23.558),P=0.019]也高于EpCAM低表达病人。结论EpCAM在ICC病人中具有较高的表达水平且与术后长期生存、肿瘤复发及淋巴转移相关,可能成为潜在的协助ICC早期诊断及预后评估的分子标志物,可作为病人术后肿瘤复发转移的预测指标。

Objective To explore the expression of EpCAM(epithelial cell adhesion molecule)in patients with intrahepatic cholangiocarcinoma(ICC)and explore its relationship with prognosis,recurrence and lymphatic metastasis.Methods Clinicopathological and prognostic data were retrospectively reviewed for 42 ICC patients undergoing surgery from January 2015 to December 2017.The expression level of EpCAM was detected by immunohistochemistry stain and the correlations between EpCAM and prognosis,recurrence and metastasis were analyzed.Results In 42 cases of ICC tumor tissue,proportion of EpCAM high expression group accounted for 85.7%(36/42).Among them,patients with a high expression level of EpCAM had a tumor recurrence rate of over 90.0%and EpCAM expression level was significantly correlated with lymphatic metastasis(r=0.356,P=0.021).In addition,Log-rank univariate survival analysis indicated that 3-year overall survival(30.6%vs.83.3%,χ^(2)=4.043,P=0.044),3-year disease-free survival(16.7%vs.66.7%,χ^(2)=4.599,P=0.032),5-year overall survival(22.2%vs.83.3%,χ^(2)=6.355,P=0.012)and 5-year disease-free survival(11.1%vs.66.7%,χ^(2)=7.006,P=0.008)of ICC patients with a high expression level of EpCAM was significantly lower than those with a low expression level of EpCAM.Cox multivariate survival analysis revealed that expression level of EpCAM was an independent predictor for 3-year disease-free survival(P=0.030),5-year overall survival(P=0.041)and 5-year disease-free survival(P=0.019)of ICC postoperative patients.The 3-year recurrence risk[HR=4.902,95%CI(1.162,20.679),P=0.030],5-year mortality risk[HR=8.069,95%CI(1.094,59.532),P=0.041]and 5-year recurrence risk[HR=5.594,95%CI(1.328,23.558),P=0.019]of ICC patients with a high expression level of EpCAM were higher than those with a low expression level of EpCAM.Conclusion With a high expression level in ICC patients,EpCAM is associated with long-term postoperative survival,recurrence and lymphatic metastasis.It may become a potential molecular marker for assisting the early diagnosis and prognosis assessment of ICC.Also it serves as a predictor of tumor recurrence and metastasis of postoperative patients.