摘要
目的:研究STAT3蛋白在精原细胞瘤中的表达,证实STAT3是否在精原细胞瘤的发生中起到诱发和推动的作用;通过对VEGF和C-myc基因的研究了解JAK/STAT3信号途径在肿瘤增殖中的作用;通过对HIWI基因以及Bcl-XL基因表达的研究,证实STAT3/Bcl-XL在肿瘤发展中抗凋亡的作用,为临床在精原细胞瘤的治疗中以STAT3为靶点开僻新方法提供必要的理论基础。
方法:应用免疫组织化学S-P法,检测STAT3,VEGF,C-myc,Bcl-xl蛋白在38例精原细胞瘤和10例正常睾丸组织中的表达;应用mRNA原位分子杂交技术,检测HIWI基因在精原细胞瘤中的转录情况。
结果:
1.STAT3,VEGF,C-myc,Bcl-xl蛋白在精原细胞瘤中的阳性表达率分别为76.3%,71.1%,84.2%,71.1%,与正常睾丸中相应基因的表达均具有显著性统计学差异(p<0.01),且上述基因与精原细胞瘤的TNM临床分期具有相关性。
2.HIWImRNA在精原细胞瘤中的阳性表达率为68.4%,与正常组织相比具有统计学差异(p<0.05),但是其阳性率与临床分期无关。
3.STAT3,VEGF,C-myc,Bcl-xl,HIWI基因之间存在不同程度的相关性:STAT3与VEGF呈正相关(r=0.640,p<0.01);STAT3与C-myc呈正相关(r=0.408,p<0.05);C-myc与VEGF呈正相关(r=0.459,p<0.01);HIWI与STAT3呈正相关(r=0.679,p<0.01);HIWI与BCL-xl呈正相关(r=0.602,p<0.01);STAT3与Bcl-xl呈正相关(r=0.669,p<0.01)。
结论:
1. JAK/Stat3信号转导途径可能激活VEGF的表达推动精原细胞瘤的发展与转移。
2. JAK/Stat3信号转导途径可能激活C-myc的表达引起生殖细胞的恶性增殖,诱导精原细胞瘤的发生与发展。
3.精原细胞瘤中,HIWI基因可能激活STAT3/Bcl-xl信号通路,赋予肿瘤细胞自我更新和抗凋亡的能力。
Objective: By studying the expression of Stat3 in seminoma, to confirm wether Stat3 play a role in the occurring of seminoma by the effection of induce and impulse;By the research on VEGF and C-myc ,understand the hyperplasy caused by the JAK/STAT3 signal transduction pathway in this tumor;By the investigation in HIWI and Bcl-xl, confirm the anti-apoptosis effection caused by STAT3/Bcl-xl in the development of seminoma,so,the aim of this topic is to provide an necessary theory basement for the clinic therapy in seminoma ,which is to aim directly at STAT3.
Methods: 38 paraffin specimen of seminoma and 10 paraffin specimen of nomal human testis were collected.IHC were used to detect the protein of Stat3、VEGF、C-myc and Bcl-xl; ISH were used to observe the mRNA transcription of HIWI .
Results:
1.The positive expression rate of STAT3、VEGF、C-myc and Bcl-xl is 76.3%、71.1%、84.2%、71.1%,and comparing nomal testis they all had different significance in statistics(p<0.01),and these genes all have relationship with the TNM clinical stage.
2.The positive expression rate of HIWImRNA was 68.4%,comparing nomal testis it had different significance in statistics(p<0.05).But it was none of the business of the TNM clinical stage.
3.There were correlation among STAT3、VEGF、C-myc、Bcl-xl and HIWI genes.There was positive correlation between STAT3 and VEGF(r=0.640,p<0.01), STAT3 and C-myc(r=0.408,p<0.05),C-myc and VEGF(r=0.459,p<0.01),HIWI and STAT3(r=0.679,p<0.01),HIWI and BCL-xl(r=0.602,p<0.01),STAT3 and Bcl-xl(r=0.669,p<0.01).
Conclusions:
1.The JAK/STAT3 signal transducer pathway could activate the expression of VEGF,and impulse the development of seminoma.
2.The JAK/STAT3 signal transducer pathway could increase the expression of C-myc and cause the malignancy hyperplasy of germinal cell,which provocating the seminoma.
3.In seminoma,the gene HIWI could activation the STAT3/Bcl-xl signal transducer pathway,give tumor cell the ability of self-renewal and anti-apoptosis.
引文
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