食管癌及Barrett食管组织抑癌基因SLC5A8甲基化状态的检测

Tumor-suppressor gene SLC5A8 methylation status in esophageal carcinoma and Barrett's esophagus tissues

目的:探讨食管癌及其癌前病变Barrett食管组织中抑癌基因SLC5A8甲基化状态及表达情况。方法:分别采用甲基化特异性PCR法(MSP)及RT-PCR法检测45例食管癌、癌旁及切缘组织SLC5A8甲基化及基因表达情况;采用MSP法检测42例Barrett食管及其正常食管黏膜中SLC5A8甲基化情况。结果:45例食管癌组织的甲基化阳性率显著高于癌旁及切缘组织,χ2=31.3,P<0.01。42例Barrett食管甲基化阳性率显著高于其正常食管黏膜,χ2=8.23,P<0.01。食管癌的甲基化阳性率与Barrett食管的甲基化阳性率之间差异有统计学意义,χ2=9.59,P<0.01。31例SLC5A8甲基化阳性的食管癌组织中仅有2例检测到SLC5A8表达;而14例阴性标本中有10例检测到SLC5A8表达,甲基化与SLC5A8表达呈负相关,r=-0.572。SLC5A8甲基化阳性的食管癌组织中SLC5A8基因表达率显著低于甲基化阴性的食管癌组织,χ2=21.17,P<0.001。结论:抑癌基因SLC5A8的甲基化率在食管正常黏膜、Barrett食管、食管癌的不同病理进展阶段呈现升高趋势,而SLC5A8表达则呈下降趋势。甲基化是使其失活而抑制SLC5A8表达的重要因素,并且可能是食管癌发生及Barrett食管演变为食管癌的一个早期分子事件。

OBJECTIVE：To study the methylation and expression status of tumor-suppressor gene SLC5A8 in esophageal carcinoma and Barrett＇s esophagus tissues. METHODS：Methylation-specific PCR （MSP） and RT-PCR were used to analyze the SLC5A8 gene methylation and expression status in 45 cases of esophageal tumor tissue,adjacent tissue and cutting edge tissue,respectively. MSP was used to analyze the SLC5A8 gene methylation in 42 cases of Barrett＇s esophagus and their matched normal esophageal mucosa. RESULTS：The frequency of methylation in tumor tissue was remarkably higher than that in adjacent tissue and cutting edge tissue （χ2=31.3,P〈0.01）. The frequency of methylation in Barrett＇s esophagus was significantly higher than that in their matched normal mucosa （χ2=8.23,P〈0.01）. The frequency of methylation in esophageal carcinoma was significantly higher than that in Barrett＇s esophagus （χ2=9.59,P〈0.01）.The expression of SLC5A8 gene in methylation-positive esophageal carcinoma was significantly lower than that in methylation-negative esophageal carcinoma （χ2 =21.17,P〈0.001）. SLC5A8 was expressed in 2 cases of 31 cases with SLC5A8 methylation,and expressed in 10 cases of 14 cases without SLC5A8 methylation. The correlation of SLC5A8 methylation status and its expression was negative （r= -0.572）. CONCLUSIONS：The methylation of SLC5A8 is elevated along with the pathological progression from normal esophageal mucosa,Barrett＇s esophagus to esophageal carcinoma.It＇s expression is down-regulated in esophageal carcinoma. Methylation is an important mechanism in inhibiting its expression. It＇s an important early molecular event in the tumorigenesis of esophageal carcinoma and the transition from Barrett＇s esophagus to esophageal carcinoma.