上皮细胞粘附分子是肝内胆管癌的一种预后标志物。

Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma.

作者信息

Sulpice Laurent, Rayar Michel, Turlin Bruno, Boucher Eveline, Bellaud Pascale, Desille Mireille, Meunier Bernard, Clément Bruno, Boudjema Karim, Coulouarn Cédric

机构信息

Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.

Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.

出版信息

J Surg Res. 2014 Nov;192(1):117-23. doi: 10.1016/j.jss.2014.05.017. Epub 2014 May 10.

DOI:10.1016/j.jss.2014.05.017

PMID:24909871

Abstract

BACKGROUND

Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.

METHODS

Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.

RESULTS

Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).

CONCLUSIONS

Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.

摘要

背景

最近，我们鉴定出了肝内胆管癌（ICC）基质的基因特征，并证明了其与预后的临床相关性。上调最明显的基因包括上皮细胞粘附分子（EpCAM），它是癌症干细胞（CSC）的一种生物标志物。我们假设CSC生物标志物可以预测切除的ICC的复发情况。

方法

对先前获得的基质特征进行功能分析，并对40例切除的ICC进行免疫组织化学检测。通过单因素和多因素分析评估CSC标志物表达与包括生存在内的临床病理因素之间的关系。

结果

ICC基质的基因表达谱突出了胚胎干细胞特征。组织微阵列上的免疫组织化学显示，与非肿瘤性纤维肝组织相比，ICC基质中CSC生物标志物的蛋白水平表达增加。ICC基质中EpCAM的过表达是总生存（风险比=2.6；95%置信区间，1.3 - 5.1；P = 0.005）和无病生存（风险比=2.2；95%置信区间，1.2 - 4.2；P = 0.012）的独立危险因素。此外，非肿瘤性纤维肝组织中EpCAM的过表达与较差的无病生存密切相关（P = 0.035）。