RaplGAP蛋白在甲状腺乳头状癌中的表达及其甲基化水平

Expression of Rapl GAP and its methylation status in papillary thyroid carcinoma

应用免疫组织化学方法，检测RaplGAP蛋白在甲状腺乳头状癌肿瘤组织及其癌旁组织中的表达情况，并运用甲基化特异性PCR方法进行RaplGAP基因启动子区甲基化水平检测。结果显示，在69例检测样本中，有54例（78％）甲状腺乳头状癌患者的肿瘤组织RaplGAP蛋白表达较癌旁组织下调；RaplGAP蛋白的下调与患者的美国癌症联合委员会（AJCC）分期T值密切相关（P=0．043）。甲基化分析发现，54例RaplGAP表达下调的甲状腺乳头状癌中46例出现甲基化（66．7％），15例表达水平无明显变化的甲状腺乳头状癌中1例出现甲基化（6．67％），二者对比差异有统计学意义（P〈0．01）；同时69例癌旁正常组织未检测到甲基化。提示基因启动子区的甲基化改变可能是RaplGAP蛋白表达下调的重要机制之一。

The expression of Rapl GAP protein was detected in 69 cases of papillary thyroid carcinoma and adjacent normal thyroid tissues with immunohistochemistry method. Methylation of Rapl GAP gene was analyzed by methylation-specific-PCR （MSP） in these tissues. The immunohistochemistry results indicated that the Rapl GAP protein was down-regulated in tumor tissues of 54 （78%） cases compared with normal thyroid tissues. Statistical analysis demonstrated that the decreased level of Rapl GAP protein expression was significantly correlated with the tumor stage T according to American Joint Committee on Cancer（ AJCC, P= 0. 043 ）. The MSP results demonstrated that 46 cases of Rapl GAP gene methylation were detected in 54 cases with down-regulated expression of Rapl GAP （66.7%）, but only 1 case of methylation was found in 15 cases without obvious change of RaplGAP expression （6.67%）, showing significant difference （P〈0.01）. There was no methylation in normal thyroid tissues. These results suggest that raised methylation of promoter region may contribute to the low expression of Rapl GAP protein in papillary thyroid carcinoma.