RhoA、ROCK1、ROCK2蛋白在胰腺癌中的表达与临床病理特征的关系研究

发布时间：2018-05-09 03:41

本文选题：RhoA + ROCK1　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:胰腺癌作为恶性度最高的消化系统肿瘤之一,病情凶险,死亡率高,预后较差,虽然近年来外科手术切除率得到了很大的提高,术后并发症发生率明显下降,但其中位生存时间及五年生存率并未得到明显有效改善。研究胰腺癌恶性生长扩散方式的分子机制,探索治疗胰腺癌的新方法,具有重要的意义。Rho是Ras超家族中的一种小G蛋白,具有GTP酶活性,ROCK是Rho的主要效应分子,被Rho激活后介导下游一系列磷酸化或去磷酸化反应,参与调节了细胞增殖、骨架活动、细胞变形、运动以及粘附等生物学行为,还可调节细胞周围基质的降解与血管生成,并可抑制凋亡,与恶性肿瘤的侵袭和转移关系密切,其机制十分复杂。近期研究发现,Rho/ROCK通路在多种恶性肿瘤组织中被异常激活,并和肿瘤的恶性生物学行为有着密切相关。国内学者也已在部分恶性肿瘤中对Rho家族成员所起的作用进行了研究,但尚未见Rho/ROCK通路与胰腺癌侵袭转移的相关报道。本研究采用免疫组织化学的方法检测RhoA、ROCK1、ROCK2蛋白在胰腺癌组织和正常胰腺组织中的表达水平,分析其表达与胰腺癌临床病理特征的关系以及RhoA与ROCK1、ROCK2蛋白之间的相互关系,观察其与胰腺癌生物学行为的相关性,并结合随访资料初步探讨RhoA、ROCK1、ROCK2蛋白在胰腺癌中表达的意义及预后价值,为临床对胰腺癌诊治方向提供新的对策和理论依据。方法:1材料本实验选取河北医科大学第四医院2014年1月1日至2016年12月31日行手术治疗的胰腺癌病例的组织石蜡标本作为实验组,共58例,全部标本组织学类型均为胰腺导管腺癌。所选病例术前患者均未接受过任何的放疗、化疗及免疫治疗,纳入本研究的所有病例均具有完整的临床病历和随访资料。另选取16例胰腺浆液性囊腺瘤患者手术切除之正常胰腺组织标本作为对照组。所有标本切除离体立即固定于10%中性甲醛溶液,石蜡包埋。所有标本均由两位有经验病理医师进行病理组织学诊断。2研究方法利用免疫组织化学方法分别检测RhoA、ROCK1、ROCK2在胰腺癌癌组织与正常胰腺组织中的表达情况,利用SPSS17.0软件进行统计学方法研究分析RhoA、ROCK1、ROCK2在胰腺癌中的关系,并同时分析RhoA、ROCK1、ROCK2与胰腺癌患者的临床病理特征包括患者年龄、性别、肿瘤大小、肿瘤部位、淋巴结转移、神经受侵、脉管受侵、肿瘤TNM分期以及病理分级的关系。同时根据随访资料分析RhoA、ROCK1、ROCK2与胰腺癌预后的关系。结果:1 RhoA、ROCK1、ROCK2蛋白在胰腺癌细胞组织中的阳性表达均显著高于正常胰腺细胞组织,RhoA、ROCK1、ROCK2蛋白在胰腺癌组织中的阳性率分别为77.6%、67.2%、74.1%,在正常胰腺组织中的阳性表达率分别为18.8%、12.5%、12.5%,差异均有统计学意义(P0.05)。2 RhoA、ROCK1、ROCK2蛋白在胰腺癌细胞组织中的阳性表达与胰腺癌组织病理分级、肿瘤TNM分期以及预后有统计学差异(P0.05);RhoA、ROCK1、ROCK2蛋白在胰腺癌细胞组织中的阳性表达与胰腺癌患者的年龄、性别、肿瘤部位以及是否有脉管受侵无统计学差异(P0.05);RhoA、ROCK2蛋白的阳性表达与神经受侵之间有统计学差异(P0.05),ROCK1蛋白的阳性表达与其神经受侵无统计学差异(P0.05)。3 RhoA、ROCK1、ROCK2蛋白在胰腺癌细胞组织中阳性表达组术后半年生存率、1年生存率、2年生存率均明显低于阴性表达组,阳性表达组中位生存时间均明显短于阴性表达组,差异均有统计学意义(P0.05)。4在胰腺癌组织中,RhoA与ROCK1蛋白表达呈正相关(r=0.479,P0.05);RhoA与ROCK2蛋白表达亦呈正相关(r=0.577,P0.05);ROCK1与ROCK2蛋白表达亦呈正相关(r=0.347,P0.05)。结论:1 RhoA、ROCK1、ROCK2蛋白在胰腺癌组织中的阳性表达率明显高于正常胰腺组织。2 RhoA、ROCK1、ROCK2蛋白在胰腺癌组织中的阳性表达均与胰腺癌的发生、发展及侵袭、转移等恶性生物学行为密切相关。RhoA、ROCK1、ROCK2蛋白的阳性表达提示患者不良预后,可以作为判断胰腺癌预后的指标。3 RhoA与ROCK1、ROCK2蛋白的表达呈正相关,ROCK1与ROCK2的表达呈正相关。胰腺癌组织中可能存在Rho/ROCK信号转导通路,该通路有可能成为胰腺癌新的治疗靶点。
[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.

【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】：R735.9

【参考文献】