胃癌组织中EphA1的表达与肿瘤转移及患者生存时间的关系

The relationship between the expression of EphA1 in gastric carcinoma,metastasis and survival

背景与目的:受体酪氨酸激酶Eph基因家族在生长发育和肿瘤发生中发挥重要作用。本课题研究EPhAl在胃癌中的表达,并分析其与临床病理指标之间的联系,旨在探索EphAl基因在胃癌发生中的作用。方法:利用实时定量逆转录聚合酶链式反应(real time RT-PCR)检测胃癌组织和正常黏膜中EphA1转录子的表达。通过甲基化特异性PCR检查启动子区相关的CpG岛甲基化状态。并运用免疫组织化学染色测定细胞的EphA1蛋白表达水平。结果:EphAl转录子在34%(19/56)的样本中表达下调,25%(14/56)的样本中表达上调,41%(23/56)的样本中表达差异无统计学意义(P>0.05)。EphAl转录子表达水平与肿瘤大小(P=0.05)、分期(P=0.001)以及淋巴结转移(P-0.011)相关。在检查的15例EphAl下调的标本中,12例检出甲基化EphAl DNA;在5例上调的标本中,仅1例检出甲基化DNA;18例表达无差异的标本中,3例检出甲基化DNA(P=0.001)。145例组织标本中EphA1蛋白表达与转录子表达的临床意义相符。随访89例患者分析生存时间发现,EphA1下调者预后比上调者长(P=0.005)。结论:EphA1可能在胃癌细胞的侵袭和转移中发挥作用。

Background and purpose： Receptor tyrosine kinases of the Eph subfamily are involved in the carcinogenesis. In this study, EphA1 expression as well as associated EphAl expressions within elinicopathologic parameters were analyzed to investigate the role of EphA1 in gastric carcinoma. Methods： The expression of EphA1 transcription in gastric carcinoma tissues and corresponding normal tissues were determined by the quantitative real time reverse transcriptase polymerase chain reaction （real time RT-PCR）. The status of CpG island associated with the promoter of EphA1 were checked by methylation specific PCR （MSP） whereas the protein of EphA1 was examined through immunohistochemical staining （IHC）. Results： Down-regulation of the EphA1 transcription was detected in 19 （34%） cases, up-regulation in 14 （25%） cases, and no differences in expression were detected in 23 （41%） cases. The expression level of EphA1 transcription was associated with tumor size （P=-0.05）, stage （P=0.001） and lymph node metastasis （P=0.011）. Methylated EphA1 DNA was detected in most examined carcinomas （12/15） with EphA1 down-regulation but rarely in those with up-regulaton （1/5） or those with no difference in expression （3/18） （P=-0,001）. IHC in 145 tissue specimens showed that the clinicopathological significance of EphA1 protein was consistent with that Of mRNA. The survival analysis in 89 cases showed that patients with a down-regulation of EphA1 had a better prognosis than those with up-regulation （P=0.005）. Conclusion： EphA1 may play an important role in the invasion and metastasis of gastric carcinoma.