發(fā)布時(shí)間：2018-05-09 03:41

  本文選題：RhoA + ROCK1�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:胰腺癌作為惡性度最高的消化系統(tǒng)腫瘤之一,病情兇險(xiǎn),死亡率高,預(yù)后較差,雖然近年來(lái)外科手術(shù)切除率得到了很大的提高,術(shù)后并發(fā)癥發(fā)生率明顯下降,但其中位生存時(shí)間及五年生存率并未得到明顯有效改善。研究胰腺癌惡性生長(zhǎng)擴(kuò)散方式的分子機(jī)制,探索治療胰腺癌的新方法,具有重要的意義。Rho是Ras超家族中的一種小G蛋白,具有GTP酶活性,ROCK是Rho的主要效應(yīng)分子,被Rho激活后介導(dǎo)下游一系列磷酸化或去磷酸化反應(yīng),參與調(diào)節(jié)了細(xì)胞增殖、骨架活動(dòng)、細(xì)胞變形、運(yùn)動(dòng)以及粘附等生物學(xué)行為,還可調(diào)節(jié)細(xì)胞周?chē)|(zhì)的降解與血管生成,并可抑制凋亡,與惡性腫瘤的侵襲和轉(zhuǎn)移關(guān)系密切,其機(jī)制十分復(fù)雜。近期研究發(fā)現(xiàn),Rho/ROCK通路在多種惡性腫瘤組織中被異常激活,并和腫瘤的惡性生物學(xué)行為有著密切相關(guān)。國(guó)內(nèi)學(xué)者也已在部分惡性腫瘤中對(duì)Rho家族成員所起的作用進(jìn)行了研究,但尚未見(jiàn)Rho/ROCK通路與胰腺癌侵襲轉(zhuǎn)移的相關(guān)報(bào)道。本研究采用免疫組織化學(xué)的方法檢測(cè)RhoA、ROCK1、ROCK2蛋白在胰腺癌組織和正常胰腺組織中的表達(dá)水平,分析其表達(dá)與胰腺癌臨床病理特征的關(guān)系以及RhoA與ROCK1、ROCK2蛋白之間的相互關(guān)系,觀察其與胰腺癌生物學(xué)行為的相關(guān)性,并結(jié)合隨訪資料初步探討RhoA、ROCK1、ROCK2蛋白在胰腺癌中表達(dá)的意義及預(yù)后價(jià)值,為臨床對(duì)胰腺癌診治方向提供新的對(duì)策和理論依據(jù)。方法:1材料本實(shí)驗(yàn)選取河北醫(yī)科大學(xué)第四醫(yī)院2014年1月1日至2016年12月31日行手術(shù)治療的胰腺癌病例的組織石蠟標(biāo)本作為實(shí)驗(yàn)組,共58例,全部標(biāo)本組織學(xué)類(lèi)型均為胰腺導(dǎo)管腺癌。所選病例術(shù)前患者均未接受過(guò)任何的放療、化療及免疫治療,納入本研究的所有病例均具有完整的臨床病歷和隨訪資料。另選取16例胰腺漿液性囊腺瘤患者手術(shù)切除之正常胰腺組織標(biāo)本作為對(duì)照組。所有標(biāo)本切除離體立即固定于10%中性甲醛溶液,石蠟包埋。所有標(biāo)本均由兩位有經(jīng)驗(yàn)病理醫(yī)師進(jìn)行病理組織學(xué)診斷。2研究方法利用免疫組織化學(xué)方法分別檢測(cè)RhoA、ROCK1、ROCK2在胰腺癌癌組織與正常胰腺組織中的表達(dá)情況,利用SPSS17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)方法研究分析RhoA、ROCK1、ROCK2在胰腺癌中的關(guān)系,并同時(shí)分析RhoA、ROCK1、ROCK2與胰腺癌患者的臨床病理特征包括患者年齡、性別、腫瘤大小、腫瘤部位、淋巴結(jié)轉(zhuǎn)移、神經(jīng)受侵、脈管受侵、腫瘤TNM分期以及病理分級(jí)的關(guān)系。同時(shí)根據(jù)隨訪資料分析RhoA、ROCK1、ROCK2與胰腺癌預(yù)后的關(guān)系。結(jié)果:1 RhoA、ROCK1、ROCK2蛋白在胰腺癌細(xì)胞組織中的陽(yáng)性表達(dá)均顯著高于正常胰腺細(xì)胞組織,RhoA、ROCK1、ROCK2蛋白在胰腺癌組織中的陽(yáng)性率分別為77.6%、67.2%、74.1%,在正常胰腺組織中的陽(yáng)性表達(dá)率分別為18.8%、12.5%、12.5%,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。2 RhoA、ROCK1、ROCK2蛋白在胰腺癌細(xì)胞組織中的陽(yáng)性表達(dá)與胰腺癌組織病理分級(jí)、腫瘤TNM分期以及預(yù)后有統(tǒng)計(jì)學(xué)差異(P0.05);RhoA、ROCK1、ROCK2蛋白在胰腺癌細(xì)胞組織中的陽(yáng)性表達(dá)與胰腺癌患者的年齡、性別、腫瘤部位以及是否有脈管受侵無(wú)統(tǒng)計(jì)學(xué)差異(P0.05);RhoA、ROCK2蛋白的陽(yáng)性表達(dá)與神經(jīng)受侵之間有統(tǒng)計(jì)學(xué)差異(P0.05),ROCK1蛋白的陽(yáng)性表達(dá)與其神經(jīng)受侵無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。3 RhoA、ROCK1、ROCK2蛋白在胰腺癌細(xì)胞組織中陽(yáng)性表達(dá)組術(shù)后半年生存率、1年生存率、2年生存率均明顯低于陰性表達(dá)組,陽(yáng)性表達(dá)組中位生存時(shí)間均明顯短于陰性表達(dá)組,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。4在胰腺癌組織中,RhoA與ROCK1蛋白表達(dá)呈正相關(guān)(r=0.479,P0.05);RhoA與ROCK2蛋白表達(dá)亦呈正相關(guān)(r=0.577,P0.05);ROCK1與ROCK2蛋白表達(dá)亦呈正相關(guān)(r=0.347,P0.05)。結(jié)論:1 RhoA、ROCK1、ROCK2蛋白在胰腺癌組織中的陽(yáng)性表達(dá)率明顯高于正常胰腺組織。2 RhoA、ROCK1、ROCK2蛋白在胰腺癌組織中的陽(yáng)性表達(dá)均與胰腺癌的發(fā)生、發(fā)展及侵襲、轉(zhuǎn)移等惡性生物學(xué)行為密切相關(guān)。RhoA、ROCK1、ROCK2蛋白的陽(yáng)性表達(dá)提示患者不良預(yù)后,可以作為判斷胰腺癌預(yù)后的指標(biāo)。3 RhoA與ROCK1、ROCK2蛋白的表達(dá)呈正相關(guān),ROCK1與ROCK2的表達(dá)呈正相關(guān)。胰腺癌組織中可能存在Rho/ROCK信號(hào)轉(zhuǎn)導(dǎo)通路,該通路有可能成為胰腺癌新的治療靶點(diǎn)。
[Abstract]:Objective: pancreatic cancer is one of the most malignant digestive system tumors. The disease is dangerous, the mortality is high and the prognosis is poor. Although the surgical resection rate has been greatly improved in recent years, the incidence of postoperative complications is obviously decreased, but the survival time and the five year survival rate have not been significantly improved. The molecular mechanism of long diffusion mode is a new method to explore the treatment of pancreatic cancer. It is of great significance that.Rho is a small G protein in the Ras superfamily, with GTP enzyme activity. ROCK is the main effect molecule of Rho. After activated by Rho, it mediates a series of phosphorylation or dephosphorylation, and participates in regulating cell proliferation, skeleton activity, and cell deformation. Biological behavior such as exercise and adhesion can also regulate the degradation and angiogenesis of the surrounding matrix and inhibit apoptosis, which is closely related to the invasion and metastasis of malignant tumors. Its mechanism is very complex. Recent studies have found that the Rho/ROCK pathway is abnormally activated in a variety of malignant tumor tissues and is associated with the malignant biological behavior of the tumor. It is closely related. Domestic scholars have also studied the role of Rho family members in some malignant tumors, but there is no related reports of Rho/ROCK pathway and invasion and metastasis of pancreatic cancer. This study was used to detect the expression of RhoA, ROCK1, ROCK2 protein in pancreatic adenocarcinoma and normal pancreatic tissue by immunohistochemical method. The relationship between the expression of the pancreatic cancer and the clinicopathological features of pancreatic cancer, the relationship between RhoA and ROCK1, ROCK2 protein, the correlation between the expression of the pancreatic cancer and the biological behavior of pancreatic cancer were observed, and the meaning and prognostic value of the expression of RhoA, ROCK1, ROCK2 protein in pancreatic cancer were preliminarily discussed in combination with the follow-up data, which provided the clinical significance for the diagnosis and treatment of pancreatic cancer. New countermeasures and theoretical basis. Methods: 1 the tissue paraffin specimens from the fourth hospital of Hebei Medical University from January 1, 2014 to December 31, 2016 were selected as the experimental group of paraffin in the experimental group, and 58 cases were all of the histological types of pancreatic ductal adenocarcinoma. All the patients before the operation were not accepted any of the cases. All cases in this study had complete clinical records and follow-up data. 16 cases of pancreatic serous cystadenoma were selected as control group. All specimens were removed in vitro and fixed to 10% neutral Formaldehyde Solution and paraffin embedded. All specimens were collected. Two experienced pathologists conducted histopathological diagnosis.2 research methods using immunohistochemical method to detect the expression of RhoA, ROCK1, ROCK2 in pancreatic cancer tissues and normal pancreatic tissues. The relationship between RhoA, ROCK1, ROCK2 in pancreatic cancer was analyzed by SPSS17.0 software and Rho was analyzed by SPSS17.0 software, and Rho was analyzed at the same time. The clinicopathological features of patients with A, ROCK1, ROCK2 and pancreatic cancer include patients' age, sex, tumor size, tumor location, lymph node metastasis, nerve invasion, vascular invasion, tumor TNM staging, and pathological classification. The relationship between RhoA, ROCK1, ROCK2 and the prognosis of pancreatic cancer is analyzed according to the follow-up data. Results: 1 RhoA, ROCK1, ROCK2 protein in the patients with pancreatic cancer. The positive expression of RhoA, ROCK1, ROCK2 protein in pancreatic cancer tissues was 77.6%, 67.2%, 74.1% respectively, and the positive rate in normal pancreatic tissue was 18.8%, 12.5%, 12.5%, respectively, and the difference was statistically significant (P0.05).2 RhoA, ROCK1, ROCK2 protein in pancreas The positive expression in the cancer cells was significantly different from the histopathological classification, TNM staging and prognosis of the pancreatic cancer (P0.05). The positive expression of RhoA, ROCK1, ROCK2 protein in pancreatic cancer cells was not statistically significant (P0.05) with the age, sex, site of the tumor and the invasion of the vasculature in pancreatic cancer patients (P0.05); RhoA, ROCK2 protein There was a statistical difference between the positive expression and the nerve invasion (P0.05). The positive expression of ROCK1 protein was not significantly different from that of the nerve invasion (P0.05).3 RhoA, ROCK1, and the 1 year survival rate of the positive expression group in the pancreatic cancer cell tissues, the 1 year survival rate and the 2 year survival rate were significantly lower than those in the negative expression group, and the positive expression group was in the middle position. The survival time was significantly shorter than the negative expression group, the difference was statistically significant (P0.05).4 in pancreatic cancer tissues, RhoA and ROCK1 protein expression was positively correlated (r=0.479, P0.05); RhoA and ROCK2 protein expression was also positively correlated (r=0.577, P0.05); ROCK1 and ROCK2 protein expression was also positive correlation. Conclusion: 1 The positive expression rate in pancreatic cancer tissues is significantly higher than that of normal pancreatic tissue.2 RhoA. The positive expression of ROCK1, ROCK2 protein in pancreatic cancer tissues is closely related to the occurrence of pancreatic cancer, and the malignant biological behaviors such as development and invasion and metastasis are closely related to.RhoA, ROCK1, ROCK2 protein positive expression suggests that the patients have bad prognosis and can be used as the judgment of the pancreas. The prognostic index of cancer.3 RhoA is positively correlated with the expression of ROCK1, ROCK2 protein, and the expression of ROCK1 is positively correlated with the expression of ROCK2. There may be a Rho/ROCK signal transduction pathway in pancreatic cancer. This pathway may be a new target for the treatment of pancreatic 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(lèi)號(hào)】：R735.9

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