MEKK3和NF-κB p50、NF-κB p65在前列腺癌中的表达及意义

发布时间：2018-05-07 13:41

本文选题：前列腺癌 + 良性前列腺增生　；参考：《河北医科大学》2017年硕士论文

【摘要】：背景:前列腺癌(prostate cancer,PCa)是男性最常见的恶性肿瘤之一。世界范围内,前列腺癌的新增病例数位居所有肿瘤的第二位,而在欧美等发达国家,前列腺癌的发病率已超过了肺癌,位居男性恶性肿瘤的首位。前列腺癌的发病具有较显著的地区及种族差异,我国前列腺癌的发病率及死亡率均低于西方发达国家,但随着我国社会老龄化程度的加快、生活方式的西方化、饮食结构的改变、医疗诊断技术的提高等,我国前列腺癌的发病趋势逐年增长。因此,为明确前列腺癌的发病机制、对前列腺癌做出早期诊断、治疗及预后评估等越来越受到人们的重视。近年来,许多肿瘤标志物被发现跟前列腺癌发生、发展有关,但它的具体发病机制仍不清楚。有丝分裂原活化蛋白激酶激酶激酶3(mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3,MEKK3)在哺乳动物的各种组织中广泛表达。该蛋白激酶通过有效激活丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)和核转录因子(nuclear factor kappa B,NF-κB)信号通路等途径,参与多种肿瘤发生、发展的过程,但MEKK3在前列腺癌中的表达情况未见报道。目的:通过检测MEKK3、核转录因子p50(NF-κB p50)、核转录因子p65(NF-κB p65)蛋白在前列腺癌及良性前列腺增生(benign prostatic hyperplasia,BPH)组织中的表达情况,分析它们与前列腺癌患者临床病理特征的关系。探讨MEKK3与NF-κB信号通路在前列腺癌发生、发展中的关系及作用,为进一步阐明前列腺癌的发病机制提供理论依据。方法:应用免疫组织化学(immunohistochemistry,IHC)S-P法检测40例前列腺腺癌组织及40例良性前列腺增生组织中MEKK3、NF-κB p50、NF-κB p65蛋白的表达情况。所有实验数据应用SPSS21.0统计学软件进行统计分析,以P0.05表示差异有统计学意义。结果:1 MEKK3蛋白的表达情况:MEKK3蛋白在前列腺癌组织以及良性前列腺增生组织中均有表达,其阳性表达率分别为80.0%(32/40)、5.0%(2/40),差异具有统计学意义(p0.05)。mekk3蛋白在高中分化组(gleason评分≤7分)及低分化组(gleason评分8~10分)前列腺癌患者中的阳性表达率分别为61.1%(11/18)、95.5%(21/22),差异具有统计学意义(p0.05)。mekk3蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的阳性表达率分别为63.2%(12/19)、95.2%(20/21),差异具有统计学意义(p0.05)。2nf-κbp50蛋白的表达情况:nf-κbp50蛋白在前列腺癌组织以及良性前列腺增生组织中均有表达,其阳性表达率分别为75.0%(30/40)、35.0%(14/40),差异具有统计学意义(p0.05)。nf-κbp50蛋白在高中分化组(gleason评分≤7分)及低分化组(gleason评分8~10分)前列腺癌患者中的阳性表达率分别为50.0%(9/18)、95.5%(21/22),差异具有统计学意义(p0.05)。nf-κbp50蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的阳性表达率分别为68.4%(13/19)、81.0%(17/21),差异无统计学意义(p0.05)。3nf-κbp65蛋白的表达情况:nf-κbp65蛋白在前列腺癌组织以及良性前列腺增生组织中均有表达,其阳性表达率分别为77.5%(31/40)、2.5%(1/40),差异具有统计学意义(p0.05)。nf-κbp65蛋白在高中分化组(gleason评分≤7分)及低分化组(gleason评分8~10分)前列腺癌患者中的阳性表达率分别为61.1%(11/18)、90.9%(20/22),差异无统计学意义(p0.05)。nf-κbp65蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的阳性表达率分别为68.4%(13/19)、85.7%(18/21),差异无统计学意义(p0.05)。4mekk3、nf-κbp50、nf-κbp65蛋白在前列腺癌中表达的相关性:应用spearman秩相关分析发现,mekk3、nf-κbp50以及nf-κbp65三者在前列腺癌中的表达存在关联性,两两呈正相关关系(p0.05)。5mekk3、nf-κbp50、nf-κbp65蛋白的表达与前列腺癌患者临床病理特征的关系:应用spearman秩相关分析,mekk3、nf-κbp50、nf-κbp65蛋白的表达与前列腺体积、前列腺特异性抗原(prostatespecificantigen,psa)、年龄无相关关系(p0.05)。结论:1mekk3与nf-κbp50、nf-κbp65蛋白在前列腺癌组织中的表达明显高于前列腺增生组织,表明他们可能参与了前列腺癌发生、发展的分子机制。这提示我们MEKK3有可能成为前列腺癌诊断的一种新型肿瘤标记物,具有潜在的临床价值。2 NF-κB p50、NF-κB p65是NF-κB信号通路的主要组成成员,其表达增高提示NF-κB信号通路已被激活。MEKK3与NF-κB p50、NF-κB p65蛋白的表达两两呈正相关,表明MEKK3可能通过激活NF-κB信号通路进而启动了前列腺癌的发生、发展。3 MEKK3的表达与前列腺癌的病理组织分化、临床分期密切相关,组织分化越差、临床分期越晚MEKK3蛋白的表达量越高,这提示我们MEKK3可能成为评估前列腺癌患者预后的新指标。
[Abstract]:Background: prostate cancer (PCa) is one of the most common malignant tumors in men. In the world, the number of new cases of prostate cancer is the second of all the tumors. In Europe and the United States, the incidence of prostate cancer is more than the lung cancer. The incidence of prostate cancer is more prominent. The incidence and mortality of prostate cancer in China are lower than that of western developed countries. However, with the accelerated aging of our society, the Westernization of life style, the change of diet structure and the improvement of medical diagnosis technology, the incidence of prostate cancer in China is increasing year by year. The pathogenesis, early diagnosis, treatment and prognosis assessment of prostate cancer have been paid more and more attention. In recent years, many tumor markers have been found to be associated with the development of prostate cancer, but its specific pathogenesis is still unclear. The mitogen activated protein kinase kinase kinase 3 (mitogen-activated protein kinase/extra) Cellular signal-regulated kinase kinase kinase 3, MEKK3) is widely expressed in various mammalian tissues. The protein kinase participates in a variety of tumorigenesis by effectively activating mitogen activated protein kinase (mitogen-activated protein kinases, MAPKs) and nuclear transcription factors (nuclear factor) signaling pathways. The expression of MEKK3 in prostate cancer has not been reported. Objective: to analyze the expression of MEKK3, nuclear factor P50 (NF- kappa B P50), nuclear factor p65 (NF- kappa B p65) protein in prostate cancer and benign prostatic hyperplasia (benign prostatic) tissue, and to analyze the clinical characteristics of prostate cancer patients with prostate cancer. The relationship between MEKK3 and NF- kappa B signaling pathway in the development of prostate cancer and its role in further elucidating the pathogenesis of prostate cancer. Methods: the use of immunohistochemistry (immunohistochemistry, IHC) S-P to detect 40 cases of prostate adenocarcinoma tissue and 40 cases of benign prostatic hyperplasia tissue The expression of medium MEKK3, NF- kappa B P50, NF- kappa B p65 protein. All experimental data were statistically analyzed with SPSS21.0 statistics software, and the difference was statistically significant by P0.05. Results: the expression of 1 MEKK3 protein: MEKK3 protein was expressed in prostate cancer tissue and benign prostaglandin hyperplasia tissue, and the positive expression rate was respectively For 80% (32/40), 5% (2/40), the difference was statistically significant (P0.05), the positive expression rate of.Mekk3 protein in the high school differentiation group (Gleason score < 7) and the low differentiation group (Gleason score 8~10 score) was 61.1% (11/18) and 95.5% (21/22), and the difference was statistically significant (P0.05).Mekk3 protein in stage I + II and stage III + IV The positive expression rate of prostate cancer patients was 63.2% (12/19) and 95.2% (20/21). The difference was statistically significant (P0.05) the expression of.2nf- kappa bp50 protein: nf- kappa bp50 protein was expressed in the prostate cancer tissue and benign prostatic hyperplasia tissue, and the positive rate was 75% (30/40) and 35% (14/40), respectively. The positive rate of P0.05.Nf- kappa bp50 protein in high school differentiation group (Gleason score < 7) and low differentiation group (Gleason score 8~10 score) was 50% (9/18), 95.5% (21/22), and the difference was statistically significant (P0.05), the positive rate of.Nf- kappa bp50 protein was positive in stage I + II and stage III + IV prostate cancer patients The expression rate was 68.4% (13/19) and 81% (17/21). The difference was not statistically significant (P0.05) in the expression of.3nf- kappa bp65 protein: nf- kappa bp65 protein was expressed in prostate cancer tissue and benign prostatic hyperplasia tissue, and the positive expression rate was 77.5% (31/40) and 2.5% (1/40) respectively. The difference was statistically significant (P0.05).Nf- kappa bp65 protein in The positive rate of high school differentiation group (Gleason score < 7) and low differentiation group (Gleason score 8~10 score) was 61.1% (11/18) and 90.9% (20/22), the difference was not statistically significant (P0.05), the positive expression rate of.Nf- kappa bp65 protein in stage I + II and stage III + IV adenocarcinoma patients was 68.4% (13/19), 85.7% (18/21). The difference was not statistically significant (P0.05).4mekk3, nf- kappa bp50, and the expression of nf- kappa bp65 protein in prostate cancer: the expression of mekk3, nf- kappa bp50 and nf- kappa bp65 three were associated with the expression in prostate cancer by Spearman rank correlation analysis, 22 Cheng Zhengxiang correlation The relationship between the clinicopathological features of adenocarcinoma patients: Spearman rank correlation analysis, the expression of mekk3, nf- kappa bp50, nf- kappa bp65 protein, the prostate volume, the prostate specific antigen (prostatespecificantigen, PSA), and age no correlation (P0.05). Conclusion: 1mekk3 and nf- kappa bp50, the expression of the protein in the prostate cancer tissue is significantly higher The prostatic hyperplasia indicates that they may be involved in the molecular mechanism of the development of prostate cancer. This suggests that MEKK3 may be a novel tumor marker for the diagnosis of prostate cancer, which has a potential clinical value of.2 NF- kappa B P50, and NF- kappa B p65 is a major component of the NF- kappa B signaling pathway. The signal pathway has been activated.MEKK3 with NF- kappa B P50, NF- kappa B p65 protein expression 22 positive correlation, indicating that MEKK3 may activate the occurrence of prostate cancer by activating the NF- kappa B signaling pathway, developing.3 MEKK3 and the pathological tissue of prostate cancer, the clinical stages are closely related, the worse the tissue differentiation, the later clinical stages are more late. The higher expression level of protein suggests that MEKK3 may be a new prognostic marker for prostate cancer.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25

【参考文献】