【作者】 刘晓龙；

【导师】 单玉喜；

【作者基本信息】 苏州大学 ， 外科学， 2011， 硕士

【摘要】 背景与目的:转化生长因子β(transforming growth factor beta,TGF-β)信号转导通路在肿瘤的发生、发展进程中发挥着重要作用,TGF-β受体的变异或缺失将导致其抑制肿瘤作用的丧失。已有研究显示膀胱癌中TGFBR1和TGFBR2的表达是下降的,而作为TGF-β信号通路中辅助受体的TGFBR3基因在膀胱癌组织中表达情况尚不清楚。本实验旨在探索膀胱尿路上皮癌中TGFBR3表达,同时观察TGFBR3异常表达与肿瘤病理分级、临床分期、淋巴结转移及患者性别等的相关性。方法:32对膀胱尿路上皮癌及癌旁组织均来自外科手术标本。应用免疫组织化检测膀胱癌组织以及癌旁膀胱组织中TGFBR3蛋白的表达。同时采用实时荧光定量PCR(Real-time PCR)检测本组膀胱癌及癌旁组织中TGFBR3 mRNA的表达。分析TGFBR3的表达与病理分级、临床分期、淋巴结转移及患者性别等的关系。结果:本组32对样本研究显示TGFBR3蛋白在膀胱癌组织中的表达阳性率为25.00%(8/32),显著低于癌旁组织78.13%(25/32),差异有统计学意义(P<0.05)。TGFBR3 mRNA在膀胱癌及癌旁组织中均有表达,在癌组织中平均相对表达量为2.25±0.65,显著低于癌旁组织6.42±1.53,差异有统计学意义(P<0.05)。在I、II、III级膀胱癌组织中TGFBR3 mRNA表达量分别为:4.15±1.69、1.96±0.68和0.90±0.65,表达量随肿瘤的病理分级的逐渐升高而减少,但组间比较差异无统计学意义(P>0.05);在非肌层浸润性膀胱癌(Tis-T1)中TGFBR3 mRNA表达量为1.94±0.76,肌层浸润性膀胱癌(T2-T4)为2.46±0.97,差异无统计学意义(P>0.05)。TGFBR3 mRNA表达量在有淋巴结转移的患者为6.05±2.55,而在无淋巴结转移的患者表达量明显降低为1.37±0.42,差异有统计学意义(P<0.05);男性患者癌组织中TGFBR3 mRNA表达量为2.25±0.72,女性患者为2.26±1.42,差异无统计学意义(P>0.05)。结论:在蛋白和mRNA水平上检测,膀胱癌组织中TGFBR3的表达量显著低于癌旁膀胱组织,显示了该基因的表达缺失在膀胱癌的发生、发展中起一定的作用。癌组织中TGFBR3 mRNA的表达量随肿瘤恶性程度的逐渐升高而减少,可能在膀胱癌的形成初期该基因起抑癌作用;TGFBR3 mRNA的表达量随肿瘤临床分期的升高而增加,尤其是在淋巴结转移的患者中表达量显著高于无淋巴结转移者,提示在膀胱癌形成后,该基因起促癌作用。更多还原

【Abstract】 Background and Objective: The transforming growth factor beta (TGF-β) signalling system plays an important role in the carcinogenesis of the bladder. Alterations in many components of the TGF-βsignaling pathway, such as mutation or deletion of receptors and other signaling components are frequent events in human cancers and lead to a loss of the tumor suppressor function of that pathway. As we known: the TGF-βreceptor I and II (TGFBR1, TGFBR2) are lost in bladder cancer at the protein level. However, the expression of TGF-βreceptor III (TGFBR3) remains unclear. In this study we investigate the expression of TGF-βreceptor III (TGFBR3) in urothelial carcinoma of the bladder (BUC); and analyze its relevance with grade, stage, and other clinical parameters in BUC.Methods: Fresh tissues and adjacent normal bladder tissues were obtained from 32 patients with BUC. TGFBR3 expression was measured by immunohistochemistry and real-time PCR. And its potential clinical significance was analyzed.Results: The TGFBR3 protein was expressed 25.00%(8/32)in BUC and 78.13%(25/32)in adjacent normal tissues(P<0.05). Lower expression of TGFBR3 mRNA was detected in BUC (2.25±0.65) than in adjacent normal tissues (6.42±1.53,P<0.05). Respectively, expression level of TGFBR3 mRNA in grade I, II, III was 4.15±1.69, 1.96±0.68 and 0.90±0.65; in stage Tis-Tl,T2-T4 was 1.94±0.76 and 2.46±0.97. TGFBR3 mRNA expression in patients with and without lymph nodes metastasis was 6.05±2.55 and 1.37±0.42. Expression of TGFBR3 mRNA in male and female group was 2.25±0.72 and 2.26±1.42. TGFBR3 mRNA level did not correlate with grade, stage and gender (P>0.05). Higher level of expression was associated with lymph nodes metastasis (P<0.05). Conclusion: Our study showes that TGFBR3 is significantly down-regulated in BUC than in adjacent normal bladder tissues, and different levels of TGFBR3 mRNA in patients with and without lymph nodes metastasis are found. So TGFBR3 may play an important role in the pathogenesis and development of BUC.更多还原