Aurora-A在食管鳞癌及癌前病变中的表达特点和研究意义

Study on the Expression and Significance of Aurora- A in Esophageal Squamous Cell Carcinoma and Precancerous Lesions

目的探讨极光激酶(aurora kinases A,Aurora-A)在食管鳞癌及癌前病变(主要为癌旁癌前病变)组织样本中的表达特征及其在食管鳞癌发生、发展过程中的作用。方法应用组织芯片技术和免疫组织化学方法(S-P法)检测Aurora-A在9例重度不典型增生组织和122例食管鳞癌组织以及它们的癌旁癌前病变组织中的表达情况;并使用实时荧光定量PCR法检测Aurora-A基因在8对癌前病变组织和5对早期食管癌组织中的表达水平;同时运用蛋白免疫印迹法和实时荧光定量PCR法检测Aurora-A基因在各细胞株(人食管上皮永生化细胞株及食管鳞癌细胞株)中的差异性表达情况。结果免疫组化结果显示Aurora-A在正常食管黏膜上皮、轻度不典型增生、中度不典型增生、重度不典型增生及食管鳞癌组织中的阳性率分别为17.2%、27.6%、50.0%、71.2%和84.3%,其表达率随病变程度加重而递增。Aurora-A基因mRNA水平在8例癌前病变组织和5例早期食管癌组织中的表达程度也明显高于其相应正常组织,其中病变组织存在Aurora-A显著性高表达的比率分别为75.0%(6/8)和60.0%(3/5)。与人食管上皮永生化细胞株相比,Aurora-A在ESCC细胞株中的表达水平也明显升高。结论Aurora-A激酶表达水平与食管癌癌前病变严重程度呈正相关(r=0.548,P=0.000),提示Aurora-A可能参与食管鳞癌的发生与发展,有望为食管鳞癌的早期诊断及治疗提供新的方向。

Objective To investigate the expression and function of Aurora Kinases A（Aurora - A） in esophageal squamous cell carcinoma （ESCC） and its precursor lesions （ most of which are tissues adjacent to carcinoma）. Methods We used tissue microarray and immunohistochemistry to detect the expression patterns of Aurora - A in 9 cases of severe dysplasia and 122 cases of ESCC combined with adjacent precursor lesions. The expression of Aurora - A in 8 cases of precancerous tissues and 5 cases of early esophageal cancer tissues were detected by Real - time PCR. The expression of Aurora - A in different cell lines （ immortalized esophageal epithelium cell lines and ESCC cell lines） were detected by Western blotting and Real - time PCR. Results The positive rate of Aurora - A in normal esophageal epithelium, mild dysplasia, moderate dysplasia, severe dysplasia and ESCC was 17.2% , 27.6% , 50.0% , 71.2% and 84.3% , separately. A progressive increase was along with the grade of the lesions. At the mRNA level, Aurora -A also expressed higher in 8 cases of precancerous tissues and 5 cases of early esophageal cancer tissues than in normal tissues with a significantly rate of 75.0% （ 6/8 ） and 60.0% （3/5） , respectively. Compared with immortalized esophageal epithelium cell lines, Aurora - A was significantly overexpressed in ESCC cell lines. Conclusion Aurora - A expression was up - regulated with the increasing grade of esophageal lesion （ r = 0. 548, P = 0. 000） , which indicated Aurora - A could be involved in the development and progression of ESCC. Aurora - A might provide a new way for early diagnosis and treatment of ESCC in the future.