發(fā)布時(shí)間：2018-05-07 13:41

  本文選題：前列腺癌 + 良性前列腺增生　； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:前列腺癌(prostate cancer,PCa)是男性最常見的惡性腫瘤之一。世界范圍內(nèi),前列腺癌的新增病例數(shù)位居所有腫瘤的第二位,而在歐美等發(fā)達(dá)國家,前列腺癌的發(fā)病率已超過了肺癌,位居男性惡性腫瘤的首位。前列腺癌的發(fā)病具有較顯著的地區(qū)及種族差異,我國前列腺癌的發(fā)病率及死亡率均低于西方發(fā)達(dá)國家,但隨著我國社會(huì)老齡化程度的加快、生活方式的西方化、飲食結(jié)構(gòu)的改變、醫(yī)療診斷技術(shù)的提高等,我國前列腺癌的發(fā)病趨勢(shì)逐年增長。因此,為明確前列腺癌的發(fā)病機(jī)制、對(duì)前列腺癌做出早期診斷、治療及預(yù)后評(píng)估等越來越受到人們的重視。近年來,許多腫瘤標(biāo)志物被發(fā)現(xiàn)跟前列腺癌發(fā)生、發(fā)展有關(guān),但它的具體發(fā)病機(jī)制仍不清楚。有絲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)在哺乳動(dòng)物的各種組織中廣泛表達(dá)。該蛋白激酶通過有效激活絲裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)和核轉(zhuǎn)錄因子(nuclear factor kappa B,NF-κB)信號(hào)通路等途徑,參與多種腫瘤發(fā)生、發(fā)展的過程,但MEKK3在前列腺癌中的表達(dá)情況未見報(bào)道。目的:通過檢測(cè)MEKK3、核轉(zhuǎn)錄因子p50(NF-κB p50)、核轉(zhuǎn)錄因子p65(NF-κB p65)蛋白在前列腺癌及良性前列腺增生(benign prostatic hyperplasia,BPH)組織中的表達(dá)情況,分析它們與前列腺癌患者臨床病理特征的關(guān)系。探討MEKK3與NF-κB信號(hào)通路在前列腺癌發(fā)生、發(fā)展中的關(guān)系及作用,為進(jìn)一步闡明前列腺癌的發(fā)病機(jī)制提供理論依據(jù)。方法:應(yīng)用免疫組織化學(xué)(immunohistochemistry,IHC)S-P法檢測(cè)40例前列腺腺癌組織及40例良性前列腺增生組織中MEKK3、NF-κB p50、NF-κB p65蛋白的表達(dá)情況。所有實(shí)驗(yàn)數(shù)據(jù)應(yīng)用SPSS21.0統(tǒng)計(jì)學(xué)軟件進(jìn)行統(tǒng)計(jì)分析,以P0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1 MEKK3蛋白的表達(dá)情況:MEKK3蛋白在前列腺癌組織以及良性前列腺增生組織中均有表達(dá),其陽性表達(dá)率分別為80.0%(32/40)、5.0%(2/40),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。mekk3蛋白在高中分化組(gleason評(píng)分≤7分)及低分化組(gleason評(píng)分8~10分)前列腺癌患者中的陽性表達(dá)率分別為61.1%(11/18)、95.5%(21/22),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。mekk3蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的陽性表達(dá)率分別為63.2%(12/19)、95.2%(20/21),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。2nf-κbp50蛋白的表達(dá)情況:nf-κbp50蛋白在前列腺癌組織以及良性前列腺增生組織中均有表達(dá),其陽性表達(dá)率分別為75.0%(30/40)、35.0%(14/40),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。nf-κbp50蛋白在高中分化組(gleason評(píng)分≤7分)及低分化組(gleason評(píng)分8~10分)前列腺癌患者中的陽性表達(dá)率分別為50.0%(9/18)、95.5%(21/22),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。nf-κbp50蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的陽性表達(dá)率分別為68.4%(13/19)、81.0%(17/21),差異無統(tǒng)計(jì)學(xué)意義(p0.05)。3nf-κbp65蛋白的表達(dá)情況:nf-κbp65蛋白在前列腺癌組織以及良性前列腺增生組織中均有表達(dá),其陽性表達(dá)率分別為77.5%(31/40)、2.5%(1/40),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。nf-κbp65蛋白在高中分化組(gleason評(píng)分≤7分)及低分化組(gleason評(píng)分8~10分)前列腺癌患者中的陽性表達(dá)率分別為61.1%(11/18)、90.9%(20/22),差異無統(tǒng)計(jì)學(xué)意義(p0.05)。nf-κbp65蛋白在Ⅰ期+Ⅱ期及Ⅲ期+Ⅳ期前列腺癌患者中的陽性表達(dá)率分別為68.4%(13/19)、85.7%(18/21),差異無統(tǒng)計(jì)學(xué)意義(p0.05)。4mekk3、nf-κbp50、nf-κbp65蛋白在前列腺癌中表達(dá)的相關(guān)性:應(yīng)用spearman秩相關(guān)分析發(fā)現(xiàn),mekk3、nf-κbp50以及nf-κbp65三者在前列腺癌中的表達(dá)存在關(guān)聯(lián)性,兩兩呈正相關(guān)關(guān)系(p0.05)。5mekk3、nf-κbp50、nf-κbp65蛋白的表達(dá)與前列腺癌患者臨床病理特征的關(guān)系:應(yīng)用spearman秩相關(guān)分析,mekk3、nf-κbp50、nf-κbp65蛋白的表達(dá)與前列腺體積、前列腺特異性抗原(prostatespecificantigen,psa)、年齡無相關(guān)關(guān)系(p0.05)。結(jié)論:1mekk3與nf-κbp50、nf-κbp65蛋白在前列腺癌組織中的表達(dá)明顯高于前列腺增生組織,表明他們可能參與了前列腺癌發(fā)生、發(fā)展的分子機(jī)制。這提示我們MEKK3有可能成為前列腺癌診斷的一種新型腫瘤標(biāo)記物,具有潛在的臨床價(jià)值。2 NF-κB p50、NF-κB p65是NF-κB信號(hào)通路的主要組成成員,其表達(dá)增高提示NF-κB信號(hào)通路已被激活。MEKK3與NF-κB p50、NF-κB p65蛋白的表達(dá)兩兩呈正相關(guān),表明MEKK3可能通過激活NF-κB信號(hào)通路進(jìn)而啟動(dòng)了前列腺癌的發(fā)生、發(fā)展。3 MEKK3的表達(dá)與前列腺癌的病理組織分化、臨床分期密切相關(guān),組織分化越差、臨床分期越晚MEKK3蛋白的表達(dá)量越高,這提示我們MEKK3可能成為評(píng)估前列腺癌患者預(yù)后的新指標(biāo)。
[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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.25

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