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乳腺癌雌激素耐药相关蛋白 1 的表达与血管内皮生长因子、p53 及食管鳞癌预后的关系。

Expression of breast cancer anti-estrogen resistance 1 in relation to vascular endothelial growth factor, p53, and prognosis in esophageal squamous cell cancer.

机构信息

Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.

出版信息

Dis Esophagus. 2013 Jul;26(5):528-37. doi: 10.1111/j.1442-2050.2012.01376.x. Epub 2012 Jul 20.

Abstract

The purpose of this study was to clarify the role of breast cancer anti-estrogen resistance 1 (BCAR1) expression in relation to vascular endothelial growth factor (VEGF), p53, and proliferation in esophageal squamous cell cancer (ESCC). Expression of BCAR1, VEGF, p53, and the ki-67 proliferative index were examined by tissue microarray and immunohistochemistry in 106 specimens with ESCC and matched adjacent normal tissues. Among them, 40 cases were simultaneously examined by Western blot. Both Western blot and immunohistochemistry showed that BCAR1 expression was substantially higher in ESCC than in adjacent normal tissues (P < 0.001). BCAR1 expression was significantly connected with degree of tumor differentiation, with poorly differentiated tumors showing higher BCAR1 expression (P < 0.001). BCAR1 expression was significantly and positively correlated with VEGF and p53 expression levels (r= 0.541, P < 0.001; r= 0.374; P < 0.001) but not proliferative index (r= 0.44; P= 0.066). Additionally, a significant relationship was also observed between VEGF and p53 (r= 0.321; P= 0.001). Kaplan-Meier survival analysis revealed that patients with high BCAR1 expression had significantly shorter survival times than those with low BCAR1 expression levels (median survival 40 months vs. 27 months, P= 0.09). Multivariate analysis also revealed that levels of BCAR1 expression (hazard ratio 2.250, P= 0.015) was a significant and independent prognostic indicator. High expression of BCAR1 is associated with elevated VEGF and p53 expression levels, as well as poor prognosis in ESCC. Therefore, BCAR1 may be a potential candidate for predicting prognosis and a new therapy target for ESCC.

摘要

本研究旨在阐明乳腺癌雌激素抵抗蛋白 1(BCAR1)表达与血管内皮生长因子(VEGF)、p53 和增殖在食管鳞状细胞癌(ESCC)中的作用。通过组织微阵列和免疫组织化学方法,在 106 例 ESCC 及匹配的相邻正常组织标本中检测了 BCAR1、VEGF、p53 和 ki-67 增殖指数。其中 40 例同时进行了 Western blot 检测。Western blot 和免疫组化均显示 BCAR1 在 ESCC 中的表达明显高于相邻正常组织(P<0.001)。BCAR1 表达与肿瘤分化程度显著相关,低分化肿瘤的 BCAR1 表达更高(P<0.001)。BCAR1 表达与 VEGF 和 p53 表达水平呈显著正相关(r=0.541,P<0.001;r=0.374;P<0.001),但与增殖指数无关(r=0.44;P=0.066)。此外,VEGF 和 p53 之间也存在显著相关性(r=0.321;P=0.001)。Kaplan-Meier 生存分析显示,BCAR1 高表达患者的生存时间明显短于低表达患者(中位生存 40 个月 vs. 27 个月,P=0.09)。多因素分析还显示,BCAR1 表达水平(风险比 2.250,P=0.015)是一个显著的独立预后指标。BCAR1 高表达与 ESCC 中 VEGF 和 p53 表达水平升高及预后不良相关。因此,BCAR1 可能是预测预后的潜在候选标志物和 ESCC 的新治疗靶点。

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