SERPINA3在子宫内膜癌中表达上调的临床意义及功能研究

背景与目的：SERPINA3是丝氨酸蛋白酶抑制剂超家族的一员，已有研究证实其在多种肿瘤细胞中异常表达。然而，它在子宫内膜癌中生物学功能及临床意义尚不清楚。本研究旨在探讨SERPINA3在子宫内膜癌细胞中的功能和子宫内膜癌预后评估中的价值。方法：①收集20对子宫内膜癌组织和正常子宫内膜组织，用实时定量PCR(quantitative real-time PCR)检测SERPINA3 mRNA在内膜组织中表达情况；②使用免疫组化方法，检测组织芯片(子宫内膜癌81例和正常对照37例)的SERPINA3表达情况，依据染色结果，用SPSS软件分析SERPINA3与子宫内膜癌临床病理特征之间的关系；③检测5株子宫内膜癌细胞系中SERPINA3的表达情况，选取表达量最高的HEC-1A细胞，利用小片段干扰RNA(small interfering RNA)干扰SERPINA3基因在HEC-1A细胞中的表达；④蛋白质印迹法(Western blot)和qPCR检测干扰后HEC-1A中SERPINA3基因在mRNA和蛋白水平表达情况，细胞迁移实验检测细胞运动能力的变化。结果：①SERPINA3 mRNA在内膜癌中表达明显高于对照内膜组织(n=20，P<0.05)；②免疫组化结果显示SERPINA3在子宫内膜癌中的表达水平高于正常子宫内膜组织(P<0.001)。SERPINA3的表达水平与子宫内膜癌的临床分期、肿瘤细胞级别、脉管浸润、淋巴结转移之间比较差异有统计学意义(P<0.05)；③干扰SERPINA3组细胞迁移能力显著减弱。结论：SERPINA3基因在子宫内膜癌中表达显著上调，可能与子宫内膜癌的侵袭和转移等相关。SERPINA3有望成为评估子宫内膜癌预后的生物学标志物，并可能作为子宫内膜癌生物靶向治疗的靶标之一。

Identify effect of SERPINA3 up-regulated expression in endometrial cancer

Background and purpose: SERPINA3 is a protease inhibitor, belonging to the serpin super family. It has been reported that SERPINA3 expression up-regulated in various tumor cells. However, its clinical significance and biological function in endometrial cancer remains unclear. This study was aimed to investigate the effect and prognosis value of up-regulated SERPINA3 (α1-ACT) in endometrial cancer. Methods: ①We collected 20 pairs of endometrial carcinoma and normal endometrial tissues then extracted total RNA, detected SERPINA3 mRNA expression by quantitative real-time PCR; ②Immunohistochemistry was used to detect the expression of SERPINA3 in tissue chip which contained 81 endometrial cancer tissue samples and 37 normal controls endometrial tissues, based on the results, using SPSS software to analyze the relationship between SERPINA3 expression with clinicopathological features of endometrial cancer;③The highest SERPINA3 expression was selected from 5 endometrial cancer cells, then small interfering RNA targeted interference SERPINA3 gene expression; ④With real-time quantitative PCR and Western blot methods, we detected SERPINA3 gene expression in mRNA and protein levels after interference, at last, analyzed cell motility by cell migration assay. Results: ①SERPINA3 mRNA expression in endometrial carcinoma was significantly higher than the control endometrial tissue (n=20, P<0.05); ②Immunohistochemistry also showed SERPINA3 expression in endometrial carcinoma higher than in normal endometrial tissues (P<0.001). The analysis showed that between the expression level of SERPINA3 with endometrial cancer clinical stage, tumor differentiation, vascular invasion, lymph node metastasis, there was a close correlation (P<0.05); ③Interference expression of SERPINA3, endometrial cancer cells migration was significantly reduced. Conclusion: SERPINA3 gene expression in endometrial carcinoma was significantly increased and correlated with endometrial cancer invasion and metastasis; SERPINA3 is expected to become the pathological marker of diagnosis and determination in the prognosis of endometrial cancer. It may be used as one of the biological target of endometrial cancer targeted therapy.