大肠癌中EGFR基因单核苷酸多态性及EGFR表达的分析

Study of EGFR expression and single nucleotide polymorphism of EGFR gene in colorectal carcinoma

目的探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)基因外显子13G64A单核苷酸多态性及EGFR蛋白表达与大肠癌的相关性。方法应用PCR-RFLP法结合DNA测序法对72例大肠癌患者外周血DNA中EGFR基因的外显子13G64A单核苷酸多态性位点的等位基因进行检测;应用免疫组织化学染色观察同组癌组织及其癌旁正常组织EGFR蛋白的表达。结果①EGFR基因外显子13 G64A多态性位点G/G、G/A、A/A基因型频率分别为27.7%、57.4%、14.9%,与淋巴结转移和TNM分期相关(P<0.05),携带G/G基因型和G等位基因的结直肠癌患者淋巴结转移风险增加;②大肠癌组织中EGFR阳性表达率分别为40.27%,癌旁正常组织EGFR阳性表达率为7.14%,大肠癌组织中EGFR表达率均明显高于癌旁正常组织(P<0.01),EG-FR的表达与大肠癌的TNM分期以及淋巴结转移情况有关(P<0.05)。结论 EGFR基因外显子13G64A单核苷酸多态性及EGFR的表达与大肠癌患者的淋巴结转移情况和预后相关,EGFR蛋白的表达与EGFR基因外显子13G64A单核苷酸多态性成正相关。

Objective To investigate the correlation between the single nucleotide polymorphism（SNP） in exon 13 G64A domain of epidermal growth factor receptor（EGFR） gene as well as EGFR expression and colorectal carcinoma.Methods Peripheral blood samples from 72 cases of colorectal carcinoma were detected for polymorphisms in exon 13 G64A domain by polymerase chain reaction restriction fragment length polymorphism（PCR-RFLP） and DNA sequencing.EGFR expressions in tumor and adjacent normal tissues were observed by immunohistochemical staining.Results ① The genotype frequencies of G/G,G/A and A/A were 27.7%,57.4% and 14.9% respectively,which had significant correlation with lymph node metastasis and TNM grade（P0.05）,genotype G/G and allele G increasing the risk of lymph node metastasis.②The expression rate of EGFR was 40.27% in cancer,7.14% in adjacent normal tissue,which was significantly different（P0.01）.Moreover,EGFR expression was associated with lymph node metastasis and TNM grade（P0.05）.Conclusions This study suggested that EGFR expression and SNP in exon 13 G64A domain of EGFR gene,both of which had positive correlation,were putatively associated with lymph node metastasis and prognosis of colorectal carcinoma.