甲状腺及乳房多原发癌病人甲状腺癌组织WIF-1基因mRNA表达及其启动子甲基化状态分析

mRNA EXPRESSION AND PROMOTER METHYLATION OF WIF-1 GENE IN THYROID CANCER TISSUES OF PATIENTS WITH MULTIPLE PRIMARY CARCINOMAS OF BREAST AND THYROID

目的探讨甲状腺、乳房多原发癌病人甲状腺癌组织WIF-1基因mRNA表达及其启动子的甲基化状态。方法采用RT-PCR及甲基化特异性PCR(MSP)方法检测33例甲状腺、乳房多原发癌病人甲状腺癌组织WIF-1基因mRNA表达及其启动子甲基化状态,以30例单纯甲状腺乳头状癌和20例甲状腺良性病变组织作为对照。结果多原发癌病人甲状腺癌组织、单纯甲状腺乳头状癌组织和甲状腺良性病变组织WIF-1基因的表达缺失率分别为51.5%(17/33)、36.7%(11/30)、15.0%(3/20),3组比较差异有统计学意义(χ2=7.105,P<0.05)。多原发癌病人甲状腺癌组织、单纯甲状腺乳头状癌组织WIF-1基因的甲基化率分别为45%(15/33)、43%(13/30),高于甲状腺良性病变组织的10%(2/20),差异有显著性(χ2=6.349、7.185,P<0.01),但多原发癌病人甲状腺癌组织与单纯甲状腺乳头状癌组织相比差异无显著性(P>0.05)。结论 WIF-1基因mRNA表达缺失在甲状腺、乳房多原发癌的发生过程中起关键作用;WIF-1基因启动子区的高甲基化状态可能是其mRNA低表达的机制之一。

Objective To investigate mRNA expression and the promoter methylation of WIF-1 gene in thyroid cancer tissue of patients with multiple primary carcinoma of thyroid （MPCT） and breast. Methods The mRNA expression and the pro- moter methylation of WIF-1 gene in 33 cases of thyroid cancer tissues in patients with multiple primary breast cancer （MPBC） and MPCT were analyzed by reverse transcription PCR （RT-PCR） and methylation specific PCR, and 30 cases of simple papillary thy- roid carcinoma （SPTC） tissues and 20 cases of benign thyroid （BT） tissues served as controls. Results The gene deletion rates of WIF-1 expressions in MPCT, SPTC and BT were 51.5% （17/33）, 36.7% （11/30） and 15.0% （3/20）, respectively, the diffe- rence between the three groups being significant （X2=7.105 ,P〈0.05）. Methylation of WlF-1 gene in MPCT and SPTC was 45% （15/33） and 43% （13/30）, respectively, which were higher than 10% （2/20） of BT, the difference being significant （X2 =6.349, 7.185;P〈〈0.01）, but there was no significant difference between MPCT and SPTC （P〉0.05）. Conclusion The absence of WIF-1 gene mRNA expression plays a key role in the process of the occurrence of multiple primary carcinomas in breast and thy roid. The promoter hypermethylation of WIF-1 gene is likely to be one of the mechanisms of low expression of its mRNA.