高迁移率族蛋白A2在胸腺癌中表达及其与临床预后关系

HMGA2 expressed in thymic carcinoma and its relationship with clinical prognosis

目的探讨高迁移率族蛋白A2(HMGA2)在胸腺癌及癌旁组织中表达及其与临床预后的关系,并探索其在胸腺癌细胞生长和转移中的作用及分子机制。方法选取海军军医大学附属长海医院自2006年1—12月收治的62例行根治性胸腺癌切除术患者术中胸腺癌组织及癌旁组织样本。利用免疫组织化学方法检验癌组织与癌旁组织中HMGA2的表达水平;通过χ2检验和Fisher精确概率法分析HMGA2对患者预后的影响;通过慢病毒构建稳定干扰HMGA2的人胸腺癌MP59和T1889细胞系,利用CCK8实验检测HMGA2对胸腺癌细胞增殖的影响;利用Transwell实验检测HMGA2对胸腺癌细胞迁移的影响;通过蛋白免疫印记和逆转录聚合酶链反应等经典生物学技术,分析筛选HMGA2调控胸腺癌细胞生长和转移的下游信号通路。结果 82.3%(51/62)患者胸腺癌组织中HMGA2的表达水平显著高于癌旁组织(P<0.05)。HMGA2高表达患者的总体存活率及无瘤存活率显著低于HMGA2低表达患者(P<0.05)。干扰HMGA2抑制胸腺癌细胞MP59和T1889的生长和迁移能力,p65分子被下调。结论 HMGA2在胸腺癌中高表达,对胸腺癌组织的生长和转移具有促进作用,其表达水平可以为判断胸腺癌患者预后提供参考。

Objective To investigate the expression of HMGA2 in thymic carcinoma tissue and its relationship with the clinical prog- nosis of patients, and explore the function of HMGA2 in thymus carcinoma and the underling molecular mechanism. Methods Collec- ting the 62 thymic carcinoma patientstissues that underwent radical resection in our hospital from January 2006 to December 2013. The expression of HMGA2 in thymic carcinoma tissue was checked by using immunohistochemical. Toanalysis the relationship HMGA2 be- tween the prognoses of patients through the Pearson chi-square test and Fisher＇s exact. Thymic carcinoma cell lines MP59 and T1889 were infected with shHMGA2 lenti-virus. The proliferation ability of MP59 shHMGA2 or T1889 shHMGA2 and their control cells were checked by CCK8 and cloning formation assay. The metastasis ability of MP59 shHMGA2 or T1889 shHMGA2 and their control cells were checked bytranswell and Invasion chamber experiment. To explore the downstream signaling pathways of HMGA2 in thymic cancer cells growth and metastasis by western blot and RT-PCRanalysis. Results HMGA2 expression was dramatically upregulated in 82. 3 % （51/62 ）thymic carcinoma patients compared with the paired non-tumorous tissues, witha lower HMGA2 expression observed in 17.7% （ 11/62 ） patients（ P 〈 0.05 ）. The overall survival and disease-free survival of HMGA2 high patients is shorter thanthe HMGA2 lower expression patients（ P 〈 0. 05 ）. Interference HMGA2 expression disrupted the growth and metastasis ability in MP59 and T1889 cells,P65 is the downstream of HMGA2 in thymus cancer cells. Conclusion High expression of HMGA2 in thymic carcinoma pro- motes the growth and metastasis of thymic carcinoma. HMGA2 may therefore prove to be a good interference target and anovel prognosis biomarker for thymic carcinoma patients.