肾癌中hepaCAM外显子2异常甲基化与hepCAM表达的关系

The Association of hepaCAM Exon 2 Aberrant Methylation and the Expression of hepaCAM in Renal Carcinoma

探讨肾癌中抑癌基因肝细胞粘附分子hepaCAM表达与hepaCAM外显子2 CpG岛甲基化状态的关系。采用甲基化敏感性限制性内切酶PCR、RT-PCR法检测肾癌细胞株(786-0,RC-2)和43例肾癌及相应的癌旁组织中hepaCAM外显子2的甲基化状态及hepaCAM mRNA的表达。786-0细胞hepaCAM表达水平低于RC-2细胞(P<0.05);786-0和RC-2细胞,前者存在hepaCAM外显子2甲基化,后者未检测到。肾癌组织中hepaCAM mRNA表达水平显著低于癌旁组织(P<0.001);肾癌组织hepaCAM外显子2的甲基化率为34.9%,癌旁组织2.33%,两者差异有显著意义(P<0.001),但在临床病理参数中的差异无统计学意义(P>0.05)。hepaCAM外显子2甲基化的肾癌组织其mRNA的表达水平显著低于未甲基化的肾癌组织(P<0.05)。因此,肾癌hepaCAM外显子2的甲基化可能是导致hepaCAM表达下降或缺失的原因之一,hepaCAM甲基化的研究为探讨肾癌发生发展的机制提供了新的理论依据。

It was to investigate the relationship between the expression of hepaCAM and methylation of hepaCAM exon 2 in renal carcinoma. Methylation-specific restrietion-PCR-assay and reverse transcription-polymerse chain reaction（ RT-PCR）were used to examine the methylation status of hepaCAM exon 2 and mRNA in renal carcinoma cell lines（786-0, RC-2）and 43 cases of renal carcinoma tissues and paired adjacent tissues. The expression of hepaCAM mRNA was down-regulated in 786-0 renal cell lines as compared with RC-2 renal cell lines（ P 〈 0.05 ） ;786-0 cell lines showed hepaCAM exon 2 methylation but RC-2 didn＇ t. The expression of hepaCAM mRNA in renal carcinomas was significant lower than that in the adjacent renal tissues（P 〈 0. 001 ）. The methylation rate of hepaCAM exon 2 was significant higher in renal carcinomas than in adjacent renal tissues（34.9% vs 2.33% ,P 〈0. 001 ）. But,there was no statistically significant difference in clinical pathology parameters （ P 〉 0.05 ）. The expression of hepaCAM mRNA was significant lower in hepaCAM exon 2 methylation renal carcinoma than that in unmetbylated renal carcinoma（P 〈 0.05）. Therefore, the methylation of hepaCAM cxon 2 seems to be one of reasons inducing the down-regulation or deletion of hepaCAM expression. The study of hepaCAM methylation provides a new theoretical evidence for the mechanism of the occurrence and development of renal carcinoma.