Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival

Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival
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EphA3在胃癌中的异常表达:与肿瘤血管生成和生存的相关性

DOI:
10.1007/s00535-012-0549-4
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发表时间:
2012-02
影响因子:
6.3
通讯作者:
Chen, Lin
Chen, Lin
中科院分区:
医学1区
文献类型:
--
作者:
Xi, Hong-Qing;Wu, Xiao-Song;Wei, Bo;Chen, Lin

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背景EphA 3是Eph受体酪氨酸激酶的成员,在肿瘤血管生成和肿瘤进展中起重要作用。然而,EphA 3在实体瘤中的功能尚未得到广泛研究。我们的目的是探讨EphA 3在胃癌中的表达,并分析其作为一个潜在的预后factor. Methods的作用,采用定量逆转录聚合酶链反应(qRT-PCR)检测EphA 3 mRNA在正常胃粘膜细胞系和胃癌细胞系。应用免疫组织化学方法检测318例胃癌组织中EphA 3和血管内皮生长因子(VEGF)的表达。CD 34免疫组化染色计数微血管密度(MVD)。采用Western blotting方法检测EphA 3在胃癌细胞株中的表达,并检测75例胃癌组织及相应正常胃黏膜组织中EphA 3和VEGF的表达。EphA 3与TNM分期及预后不良相关(均P < 0.001)。多变量分析显示EphA 3对生存率有独立影响(P= 0.037)。EphA 3与VEGF(P< 0.001)、MVD(P< 0.001)呈正相关。Westernblot分析表明,胃癌组织中EphA 3和VEGF的表达均显著高于正常黏膜组织(均P < 0.001)。结论EphA 3在胃癌的血管生成和预后中起重要作用,可能成为胃癌治疗干预的靶点和临床评估肿瘤预后的潜在指标。
BackgroundEphA3, a member of the Eph receptor tyrosine kinases, plays important roles in tumor angiogenesis and progression. However, the function of EphA3 in solid tumors has not been widely studied. We aimed to explore EphA3 expression in gastric carcinoma and analyze its role as a potential prognostic factor.MethodsQuantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess EphA3 mRNA in a normal gastric mucosa cell line and carcinoma cell lines. Immunohistochemistry for EphA3 and vascular endothelial growth factor (VEGF) was performed in 318 cases of gastric carcinoma. CD34 immunohistochemical staining was used for microvessel density (MVD) counting. Western blotting was used to analyze EphA3 expression in the cell lines and to determine the expression of EphA3 and VEGF in 75 cases of gastric carcinoma and matched normal mucosa.ResultsEphA3 mRNA and protein expression was significantly higher in gastric cancer than that in normal mucosa (allP< 0.001). EphA3 was significantly correlated with TNM stage and poor prognosis (allP< 0.001). Multivariate analysis showed that EphA3 had an independent effect on survival (P= 0.037). EphA3 was positively correlated with VEGF (P< 0.001), and MVD (P< 0.001). According to Western blot analysis, both EphA3 and VEGF expression were significantly higher in carcinoma than that in normal mucosa (allP< 0.001). A positive correlation was observed between EphA3 and VEGF expression in cancer (P< 0.001,r= 0.513).ConclusionsEphA3 may play important roles in the angiogenesis and prognosis of gastric carcinoma, and thus may become a useful target for therapeutic intervention and a potential indicator for clinical assessment of tumor prognosis.
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发表时间: 2010-04
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