【作者】 杨海霞；

【导师】 李晓鸣；

【作者基本信息】 兰州大学 ， 病理学与病理生理学专业， 2018， 硕士

【摘要】 目的:前列腺癌是男性泌尿系统最常见的肿瘤之一,病因不明,临床早期症状不明显且无特异性,往往临床发现时已处于病变晚期,治疗效果不佳。TLR4、MyD88是介导炎症反应的重要因子,TLR4通过依赖MyD88通路和非依赖MyD88通路两条途径激活NF-κB通路,NF-κB通路通过促进TNF-a,IL-1等因子的释放参与炎症反应的发生,同时,NF-κB通路还通过促进诱导型一氧化氮合酶(iNOS)的产生,调控细胞周期,抑制细胞凋亡,促进细胞增殖。近来炎症与肿瘤的关系越来越被人们所关注,关于TLR4、MyD88、iNOS与各类肿瘤的关系也得到了广泛研究。研究表明TLR4、MyD88、iNOS与乳腺癌、淋巴瘤等肿瘤的发生发展关系密切,在肿瘤细胞周期的调节方面起重要作用。关于TLR4、MyD88、iNOS与前列腺癌关系的研究,目前尚未见系统报道。本研究通过检测前列腺癌中TLR4、MyD88、iNOS的表达,试图探索TLR4、MyD88、iNOS的表达对前列腺癌发生、转移的影响。方法1.选取前列腺癌组织样本40例,前列腺增生组织样本20例,前列腺炎样本28例,采用RNAscope原位杂交法检测组织样本中TLR4 mRNA的表达,分析前列腺癌样本中TLR4 mRNA的表达与患者临床病理特征及分期的关系。2.选取前列腺癌组织标本40例,前列腺增生组织样本20例,前列腺炎样本28例,采用免疫组化法检测组织样本中TLR4、MyD88、iNOS蛋白的表达,分析前列腺癌样本中TLR4、MyD88、iNOS蛋白的表达与患者临床病理特征及分期的关系。结果1.前列腺癌中TLR4 mRNA的阳性表达高于前列腺增生TLR4 mRNA的阳性表达(p<0.05),前列腺炎中TLR4 mRNA的阳性表达高于前列腺增生中TLR4mRNA的阳性表达(p<0.05),前列腺癌、前列腺炎中TLR4 mRNA的阳性表达无明显差异(p>0.05)。且转移性前列腺癌中TLR4 mRNA的表达高于非转移性前列腺癌中的表达(p<0.05),TLR4 mRNA在前列腺癌中的高表达与前列腺癌的高Gleason分级成正相关(p<0.05),与前列腺癌患者的年龄、血清PSA浓度无关(p>0.05)。2.前列腺癌中TLR4蛋白的阳性表达高于前列腺增生TLR4蛋白的阳性表达(p<0.05),前列腺炎中TLR4蛋白的阳性表达高于前列腺增生中TLR4蛋白的阳性表达(p<0.05),前列腺癌、前列腺炎中TLR4蛋白的表达无明显差异(p>0.05),且转移性前列腺癌中TLR4蛋白的表达高于非转移性前列腺癌中TLR4蛋白的表达(p<0.05),前列腺癌中TLR4蛋白的高表达与前列腺癌的高Gleason分级成正相关(p<0.05),与前列腺癌患者的年龄、血清PSA浓度无关(p>0.05)。3.前列腺癌、前列腺增生、前列腺炎中MyD88蛋白的阳性表达水平无明显差异(p>0.05),且前列腺癌中MyD88蛋白的表达与前列腺癌所处分期、前列腺癌的Gleason分级、患者的血清PSA浓度、年龄均无关(p>0.05)。4.前列腺癌中iNOS蛋白的阳性表达高于前列腺增生、前列腺炎中i NOS蛋白的阳性表达(p<0.05),前列腺增生、前列腺炎中iNOS蛋白的表达无明显差异(p>0.05),且转移性前列腺癌中iNOS蛋白的表达低于非转移性前列腺癌中iNOS蛋白的表达(p<0.05),前列腺癌中iNOS蛋白的高表达与前列腺癌的高Gleason分级成正相关(p<0.05),与前列腺癌患者的年龄、血清PSA浓度无关(p>0.05)。5.前列腺癌中TLR4 mRNA的阳性表达与前列腺癌中TLR4蛋白的阳性表达具有相关性(p<0.05),前列腺癌中TLR4蛋白的阳性表达与前列腺癌中iNOS蛋白的阳性表达具有相关性(p<0.05),前列腺癌中TLR4蛋白的阳性表达与前列腺癌中MyD88蛋白的表达无明显相关性(p>0.05),前列腺癌中iNOS蛋白的阳性表达与前列腺癌中MyD88蛋白的表达无明显相关性(p>0.05)。结论1.前列腺癌中TLR4、iNOS的表达影响前列腺癌的发生。2.前列腺癌中TLR4、iNOS的表达影响前列腺癌的转移。3.中TLR4 mRNA的表达与前列腺癌中TLR4蛋白的表达具有相关性;前列腺癌中TLR4蛋白的表达与前列腺癌中iNOS蛋白的表达具有相关性。更多还原

【Abstract】 Objective:Prostate cancer is one of the most common tumors in the male urogenital tumors.The pathogenesis is still uncertain.It’s symptom is not obvious and particular in the early stage.The curative effect of the Prostate cancer is unsatisfactory because it was been discovered in the last stage mostly.TLR4,MyD88 is an important pathways in inflammation,TLR4 activate the NF-κB pathways by the TLR4/MyD88 pathways or another no MyD88 pathways.The iNOS,TNF-a,IL-1 and other cytokines can be secreted by NF-κB pathways to regulation of the inflammation response and the cell cycle.Nowadays,the relationship between inflammation and tumor has attracted more and more attention,and the relationship between TLR4,MyD88,iNOS and various tumors has also been extensively studied.A lot of studies shown that the TLR4,MyD88,iNOS pathways are closed to the development of the tumor,such as the Breast cancer,lymphoma.It plays a significant role in the regulation of the tumor cell cycle.It is always uncertain that the relation between the TLR4,MyD88,iNOS and the prostate cancer nowadays.In our study,we detected the expression of the TLR4,MyD88,iNOS and to explore its effect on the occurrences and metastases of the prostate cancer.Methods1 TLR4 mRNA expression were determined by RNAscope ISH in prostate cancer tissues from 40 patients.The 20 benign prostatic hyperplasia tissues and 28 prostatitis tissues as control.Expression of TLR4 mRNA was correlated with clinicopathogic parameters of the prostate cancer.2 TLR4,MyD88,iNOS expression were determined by immunohistochemistry in prostate cancer tissues from 40 patients.The 20 benign prostatic hyperplasia tissues and 28 prostatitis tissues as control.Expression of these proteins was correlated with clinicopathogic parameters of the prostate cancer.Result1 TLR4 mRNA expression in prostate cancer were higher than that in benign prostatic hyperplasia(p<0.05),TLR4 mRNA expression in prostatitis were higher than that in benign prostatic hyperplasia(p<0.05),TLR4 mRNA expression in prostate cancer,prostatitis were similarly(p>0.05),and the expression increased in the metastatic prostate cancer compared to non-metastatic prostate cancer(p<0.05).The TLR4 mRNA expression levels increased in high Gleason score prostate cancer(p<0.05),but had no connection with the age and serum PSA levels of patients(p>0.05).2 TLR4 protein expression in prostate cancer were higher than that in benign prostatic hyperplasia(p<0.05),TLR4 protein expression in prostatitis were higher than that in benign prostatic hyperplasia(p<0.05),TLR4 protein expression in prostate cancer,prostatitis were similarly(p>0.05),and the expression increased in the metastatic prostate cancer compared to non-metastatic prostate cancer(p<0.05).The TLR4 expression levels increased in high Gleason score prostate cancer(p<0.05),but had no connection with the age and serum PSA levels of patients(p>0.05).3 MyD88 protein expression in prostate cancer,benign prostatic hyperplasia and prostatitis were similarly(p>0.05),and the expression had no connection with the stage of the cancer(p>0.05).The age and serum PSA levels of patients had nothing to do with the MyD88 expression in prostate cancer(p>0.05).4 iNOS protein expression in prostate cancer were higher than that in benign prostatic hyperplasia and prostatitis(p<0.05),iNOS protein expression in benign prostatic hyperplasia and prostatitis were similarly(p>0.05),and the expression decreased in the metastatic prostate cancer compared to non-metastatic prostate cancer(p<0.05).The iNOS expression levels increased in high Gleason score prostate cancer(p<0.05),but hsd no connection with the age and serum PSA levels of patients(p>0.05).5 TLR4 mRNA expression in prostate cancer were closed to TLR4 protein expression in prostate cancer(p<0.05).TLR4 protein expression in prostate cancer were closed to iNOS protein expression in prostate cancer(p<0.05).TLR4 protein expression in prostate cancer had nothing to do with MyD88 protein expression in prostate cancer(p>0.05).iNOS protein expression in prostate cancer had nothing to do with MyD88 protein expression in prostate cancer(p>0.05).Conclusion1 The expression of TLR4 and iNOS in prostate cancer affects the occurrence of prostate cancer.2 The expression of TLR4 and iNOS in prostate cancer affects the metastasis of prostate cancer.3 Expression of TLR4 mRNA is related to the expression of TLR4 protein in prostate cancer.Expression of TLR4 protein is related to the expression of iNOS protein in prostate cancer.更多还原