AT富集序列特异性结合蛋白1在人膀胱移行细胞癌组织中的表达及其与上皮间质转化的关系

Expression of special AT rich sequence binding protein-1 in bladder transitional cell carcinoma and its correlation with epithelial-mesenchymal transition

目的观察AT富集序列特异性结合蛋白1（SATBl）与上皮一间质转化（EMT）相关基因在人膀胱移行细胞癌中的表达，探讨SATB1与EMT相关基因表达与膀胱癌病理分级、临床分期及淋巴结转移的关系。方法分别用免疫组织化学和实时定量逆转录聚合酶链反应（RT—qPCR）检测82例膀胱癌组织标本中的SATB1、E-钙黏蛋白（E—cadherin）及Snail的表达，每例标本均选用癌组织中心、癌旁组织，并选择癌组织远端正常黏膜作为对照。结果免疫组织化学显示SATB1、E—cadherin及Snail在膀胱各组标本的阳性表达率分别为：膀胱癌为90．24％、18．29％、80．49％，癌旁组织为17．07％、79．27％、30．49％，正常膀胱组织为8．54％、91．46％、15．85％，SATB1和Snail阳性表达率在膀胱癌组明显高于癌旁组织和正常膀胱组织组，E—cadhefin阳性表达率膀胱癌组明显低于癌旁组织和正常膀胱组织组，各组比较差异有统计学意义（P〈0．05）；SATBl、E—cadhefin及Snail在膀胱癌不同病理分级中的阳性表达率分别为G．组76．19％、23．81％、61．90％，G，组92．00％、20．00％、76．00％，G，组97．22％、13．89％、94．44％，差异有统计学意义（P〈0．05）；在膀胱癌不同临床分期中，SATBl、E—cadherin及Snail阳性表达率分别为：Tis～T．组为78．00％、24．24％、66．67％，T2～T4组为97．96％、14．29％、89．80％；在淋巴结转移组和非淋巴结转移组的阳性表达率为92．86％、25．00％、96．43％、88．89％、14．81％、72．22％，随着临床分期的增高和淋巴结转移的出现，SATBl和Snail表达水平逐渐升高，E—cadherin表达水平逐渐降低，各组间差异有统计学意义（P〈0．05）；RT—qPCR结果显示，SATBl和Snail基因在膀胱癌中的表达明显高于癌旁组织和正常膀胱黏膜组织，而E-cadherin在膀胱癌中的表达明显低于癌旁组织和正常膀胱黏膜组织，各组差异有统计学意义（P〈0．05），与免疫组织化学结果相符。结论SATBl和EMT相关基因表达异常与膀胱癌的分级、分期和淋巴结转移密切相关，SATBl表达与E—cadherin表达呈负相关，与Snail呈正相关，SATBl可能通过诱导EMT调节膀胱移行上皮癌的侵袭和转移过程。

Objective To investigate the expression of special AT rich sequence binding protein-1 （SATB1） and genes involved in epithelial-mesenchymal transition （EMT） in bladder transitional cell car- cinoma （BTCC） , and to explore the relationship between SATB1 and EMT-related genes with with clinico- pathologic features of BTCC. Methods Immunohistochemisty and real-time reverse transcriptase-polymer- ase chain reaction （RT-qPCR） were used to detect the expression of SATB1, E-cadherin and Snail in 82 cases of BTCC tissues. For each specimen, the cancerous tissue, peri-cancer tissue and its remote normal mucosa were analyzed and compared. Results The immunohistochemisty revealed that the expression of SATB1 and Snail in BTCC was significantly higher than that in pericarcinomatous tissues and normal blad- der tissues （ P 〈 0. 05 ）. Inversely, the expression of E-cadherin was significantly lower in BTCC than that in pericarcinomatous tissues and normal bladder tissues （P 〈 0. 05 ）. The positive expression rate of SATB1, E-eadherin and Snail was 90. 24% , 18.29% and 80. 49% for BTCC, 17. 07% , 79.27% and 30. 49% for pericarcinomatouse tissues, and 8.54% , 9l. 46% and 15.85% for normal bladder tissues, respectively. The positive expression rate of SATB1, E-eadherin and Snail in the pathological grades 1, 2 and3 was 76. 19%, 23.81% and 61.90%, 92. 00%, 20. 00% and 76.00%, and 97.22%, 13.89% and 94. 44% respectively. There were significant differences in each group （ P 〈 0. 05 ）. The positive ex- pression rate of SATB1 and Snail in the clinical stages of Tis-Tl was lower than that in the stages of T2-T4 （78.00% vs. 97.96% ,P 〈 0. 05 ; 66. 67% vs. 89. 80% ,P 〈 0. 05 ）. Inversely, the positive expression rate of E-cadherin was significantly higher in the clinical stages of Tis-TI than that in the stages of T2-T4 （24. 24% vs. 14. 29% ,P 〈0. 05）. Moreover, with the advancing grades and appearances of lymph node metastasis, the expression levels of SATB1 and Snail were increased gradually, but in contrast, the expres- sion levels of E-cadherin decreased gradually. There were significant differences in each group （P 〈 0. 05）. The results of RT-qPCR data were agreed to those of the immunohistochemisty. Conclusion The excessive expression of SATB1 and Snail, and low expression of E-eadherin were closely related to the pa- thology, clinical stages and metastasis of lymph node of the cancer. SATB1 expression was inversely corre- lated to E-cadherin, but positively to Snail. SATB1 may regulate the invasion and metastasis of BTCC through inducing EMT. The over expression of SATB1 may play an important role in carcinogenesis and progress of BTCC.