miRNAs在甲状腺乳头状癌中的表达及临床病理意义

目的：探讨甲状腺乳头状癌（PTC）中特征性的miRNA表达谱以及临床病理意义。方法对52例PTC及7例良性甲状腺肿瘤手术切除标本采用基因芯片技术及RNA印迹杂交法检测miRNA的表达，对过表达的miRNA表达水平与PTC临床病理特征之间的关系进行分析。结果（1）用基因芯片技术筛检发现 PTC 组织中5例过表达的 miRNAs（miR-375、miR-34a、miR-146b、miR-222、miR-31）。（2）RNA印迹杂交法验证芯片结果及检测其他miRNAs结果显示：miR-34a、miR-146b、miR-31、miR-21和miR-221在PTC组织中的表达水平较癌旁正常甲状腺组织显著升高（P＜0.05）。MiR-146b和miR-221在PTC组织中的过表达率较良性甲状腺肿瘤组织显著升高（P＜0.01）。PTC患者中包膜侵犯组、淋巴结转移组、TNM分期III- IV期组及AGES系统评分≥5分组miR-221的表达水平均明显高于相应对照组（P＜0.05或0.01）；而男性PTC患者的miR-146b表达水平明显高于女性PTC患者（P＜0.05）。结论 miR-146b、miR-221、miR-21和miR-31的过表达与PTC的发生、发展有关；过表达的miR-221和miR-146b与PTC的预后不良有关。

Expression of specific miRNAs in papillary thyroid carcinomas and their clinicopathological significance

Objective To investigate expression of specific miRNAs in papillary thyroid carcinoma （PTC） and their clini-copathological significance. Methods Fifty two surgical specimens of PTC tissues and 7 specimens of benign thyroid tumor tis-sues were col ected. The miRNA expression levels were detected by using microarray and Northern blot. The correlation between over- expressed miRNAs and clinicopathological features of PTC were analyzed. Results A set of 5 over- expressed miRNAs （miR- 375, miR- 34a, miR- 146b, miR- 222, miR- 31） was distinguished by microarray in PTC tissues compared to cancer- adja-cent tissues. Using Northern blot, the results of microarray were verified;and Northern blot results also showed that the expres-sion levels of miR- 34a, miR- 146b, miR- 31, miR- 221 and miR- 21 in PTC were significantly higher than those in cancer- adjacent tissues（P〈0.05）. Additional y, the over- expression rates of miR- 146b and miR- 221 in PTC tissues were significantly higher than those in benign thyroid tumor tissues （P〈0.01）. The expression levels of miR- 221 in PTC patients with extrathyroidal invasion, lymph node metastasis, advanced TNM stage （III- IV） and AGES score≥5 were significantly higher than those in control groups （P〈0.05 or 0.01）;whereas the expression level of miR- 146b in male PTC patients was significantly higher than that in female PTC patients （P〈0.05）. Conclusion Over- expression of miR- 146b, miR- 221, miR- 21, and miR- 31 may be associated with car-cinogenesis and progression of PTC, and the over- expression of miR- 221 and miR- 146b are also correlated with poor clinical outcome of PTC patients.