Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity
Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity
复制标题
DOI：
10.1038/onc.2011.59
复制
发表时间：
2011-08-01
期刊：
影响因子：
8
通讯作者：
Doki, Y.
中科院分区：
文献类型：
--
作者：
Akita, H.;Nagano, H.;Doki, Y.
识别用于预测胰腺癌患者预后的分子标志物对于疾病管理的进展至关重要。上皮细胞粘附分子（Ep-CAM）在大多数上皮性恶性肿瘤中均有表达，已被报道为肿瘤标志物或分子靶向治疗的候选者。然而，Ep-CAM在胰腺癌中表达的临床意义尚不清楚。我们通过增殖、侵袭和迁移实验来确定亲本和Ep-CAM转染的胰腺癌细胞系之间恶性潜能的差异。此外，我们确定了在两个不同的癌症中心接受根治性手术的95例胰腺癌患者的切除标本的肿瘤Ep-CAM表达和临床预后之间的关系。其中一株细胞的增殖率明显低于亲本细胞，而另两株细胞的增殖率无明显差异。在侵袭和迁移试验中，Ep-CAM转染的细胞在所有三种细胞系中显示出比亲本细胞显著更低的恶性潜能。95例胰腺癌中，47例Ep-CAM高表达，48例低表达，Ep-CAM高表达组与低表达组的临床病理特征无差异。Ep-CAM高表达组的总生存率（3年生存率; 56.2 vs 19.2%，P = 0.0018）和无病生存率（3年生存率; 40.3 vs 14.4%，P = 0.038）均显著优于低表达组。此外，当将患者分为LN阳性组和阴性组检查Ep-CAM的影响时，在LN阴性组中观察到强烈的Ep-CAM的影响。多因素分析显示，Ep-CAM表达与组织学类型、淋巴结转移无关，是影响预后的独立因素。Ep-CAM的表达与胰腺癌细胞活性的抑制和胰腺癌患者接受根治性切除术的良好预后有关。Oncogene（2011）30，3468-3476; doi：10.1038/onc.2011.59; 2011年3月14日在线发表
The identification of molecular markers useful for predicting prognosis in pancreatic cancer patients is crucial for advances in disease management. The epithelial cell adhesion molecule (Ep-CAM) is known to express in most epithelial malignancies and was reported as a tumor marker or a candidate of molecular targeting therapy. However, the clinical significance of Ep-CAM expression in pancreatic cancer is not well-known. We determined the difference of malignant potential between parental and Ep-CAM-transfected pancreatic cancer cell lines by using proliferation, invasion and migration assay. Furthermore, we determined the relationship between tumoral Ep-CAM expression of resected specimens and clinical prognosis in 95 pancreatic cancer patients receiving radical surgery at two different cancer centers. One of the three Ep-CAM-transfected cell lines showed significantly low proliferation rate compared with the parental cell, while there was no difference in the other two cell lines. In invasion and migration assays, Ep-CAM-transfected cells showed significantly lower malignant potential than parental in all of the three cell lines. In 95 pancreatic cancer patients, 47 patients showed high-Ep-CAM expression, while 48 patients showed low, and there was no difference of clinicopathological features between Ep-CAM high and low-expression group. High-Ep-CAM expression group showed significantly good prognosis in overall survival (3-year survival; 56.2 versus 19.2%, P = 0.0018) as well as in disease-free survival (3-year survival; 40.3 versus 14.4%, P = 0.038) compared with low-expression group. In addition, the impact of Ep-CAM was observed strongly in LN-negative group when the influence of Ep-CAM was examined with dividing patients into LN-positive and negative group. In multivariate analysis, Ep-CAM expression was one of the independent prognostic factors as well as histology and lymph node metastasis. Ep-CAM expression was found to be related to the suppression of pancreatic cancer cell activity and the good prognosis in pancreatic cancer patients receiving the curative resection. Oncogene (2011) 30, 3468-3476; doi:10.1038/onc.2011.59; published online 14 March 2011