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血管生成拟态及低氧诱导因子-1α/上皮钙黏蛋白的异常表达与食管鳞状细胞癌的预后较差相关。

Vasculogenic mimicry and aberrant expression of HIF-lα/E-cad are associated with worse prognosis of esophageal squamous cell carcinoma.

作者信息

Chai Da-Min, Bao Zheng-Qi, Hu Jian-Guo, Ma Li, Feng Zhen-Zhong, Tao Yi-Sheng

机构信息

Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, 233000, China.

Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2013 Jun;33(3):385-391. doi: 10.1007/s11596-013-1129-4. Epub 2013 Jun 17.

DOI:10.1007/s11596-013-1129-4
PMID:23771665
Abstract

This study aims to find good markers for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Vasculogenic mimicry (VM) and the expression of hypoxia inducible factor-lα (HIF-lα)/E-cad protein in ESCC were investigated by immunostaining. The association between VM, HIF-lα/E-cad and clinicopathologic characteristics and 5-year-survival rate of patients with ESCC was analyzed. A total of 160 ESCC specimens were involved in this study and 28 specimens of normal esophageal mucosa served as controls. VM channels were identified in 78 (48.75%) of the 160 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of high-expression of HIF-lα and E-cad in ESCC were 43.75% and 38.75%, while the rates in control were 17.86% and 71.43%, respectively (P<0.05 for all). VM and the expression levels of HIF-lα and E-cad were significantly related to lymph node metastasis, serosa infiltration, PTNM staging and 5-year-survival rates of patients with ESCC (P<0.05 for all). VM was positively correlated with HIF-lα but negatively with E-cad, and HIF-lα was negatively correlated with E-cad (P<0.001 for all). The 5-year-survival rate of patients with ESCC was 6.41% (5/78) in VM group and 65% (52/82) in non-VM group, 7.14% (5/70) in high HIF-lα expression group and 57.78% (52/90) in low HIF-lα expression group. Oppositely, the 5-year-survival rate in high E-cad expression group was 80.65% (50/62) and that in low E-cad expression group was 7.37% (7/98) (P<0.05 for all). Cox multifactor regression analysis indicated that lymph node metastasis, PTNM stage, VM and expression levels of HIF-lα and E-cad were independent risk factors of patients with ESCC (P<0.05 for all). Combined detection of VM, HIF-lα and E-cad plays an important role in predicting the invasion, metastasis and prognosis of patients with ESCC.

摘要

本研究旨在寻找预测食管鳞状细胞癌(ESCC)患者预后的良好标志物。通过免疫染色研究了ESCC中血管生成拟态(VM)以及缺氧诱导因子-1α(HIF-1α)/E-钙黏蛋白的表达情况。分析了VM、HIF-1α/E-钙黏蛋白与ESCC患者临床病理特征及5年生存率之间的关系。本研究共纳入160例ESCC标本,28例正常食管黏膜标本作为对照。在160例ESCC标本中有78例(48.75%)发现了VM通道,而正常食管黏膜中未发现有VM。ESCC中HIF-1α和E-钙黏蛋白高表达率分别为43.75%和38.75%,而对照组分别为17.86%和71.43%(均P<0.05)。VM以及HIF-1α和E-钙黏蛋白的表达水平与ESCC患者的淋巴结转移、浆膜浸润、PTNM分期及5年生存率显著相关(均P<0.05)。VM与HIF-1α呈正相关,与E-钙黏蛋白呈负相关,且HIF-1α与E-钙黏蛋白呈负相关(均P<0.001)。ESCC患者中,VM组的5年生存率为6.41%(5/78),非VM组为65%(52/82);HIF-1α高表达组为7.14%(5/70),低表达组为57.78%(52/90)。相反,E-钙黏蛋白高表达组的5年生存率为80.65%(50/62),低表达组为7.37%(7/98)(均P<0.05)。Cox多因素回归分析表明,淋巴结转移、PTNM分期、VM以及HIF-1α和E-钙黏蛋白的表达水平是ESCC患者的独立危险因素(均P<0.05)。联合检测VM、HIF-1α和E-钙黏蛋白在预测ESCC患者的侵袭、转移及预后方面具有重要作用。

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