RASA1在非小细胞肺癌组织中的表达及其临床意义

发布时间：2018-03-01 06:15

本文关键词： 非小细胞肺癌免疫组化 RAS p21蛋白活化子1　出处：《长江大学》2017年硕士论文　论文类型：学位论文

【摘要】：肺癌是最常见的恶性肿瘤,也是最主要的致死原因之一。近年来肺癌的发病率在全球范围内仍呈持续上升的趋势,在欧美的发达国家中以及我国的一些大城市中,肺癌发病率在男性恶性肿瘤中已居首位;在女性发病率也迅速增高,占女性常见恶性肿瘤的第2位或第3位,而在肺癌患者中,非小细胞肺癌(non-small cell lung cancer,NSCLC)患者约占80%以上,因此针对NSCLC的研究具有十分重要的现实意义。RAS基因突变存在于约30%的肺腺癌患者中,RAS p21蛋白活化子1(RAS p21 protein activator 1,RASA1)是RAS GTP酶激活蛋白(RAS GAPs)家族的成员之一——能够激活GTP酶,使活化的RAS蛋白转为非活化状态,终止信号转导,从而抑制肿瘤的发生。研究发现,在多种人类肿瘤中,RASA1的表达水平均有不同程度的降低,并与肺鳞状细胞癌细胞的增殖抑制有关。目的:研究RASA1在NSCLC组织及癌旁正常支气管粘膜组织中的表达情况,并结合临床资料,探讨RASA1的表达与NSCLC肿瘤的大小,组织学类型、淋巴结转移和临床分期等临床病理特征的相关性及其临床意义。方法:收集2013年3月至2016年1月期间经由长江大学附属第一医院肿瘤外科或心胸外科手术切除,由2名病理诊断医师独立诊断为NSCLC的组织标本,查阅其临床资料,选取符合纳入条件的病理标本202例作为实验组,随机抽取60例癌旁正常的支气管粘膜组织作为对照组。所有标本均经过4%的多聚甲醛灌注固定,常规石蜡包埋封存。通过比对患者的HE切片,在病理诊断医师的指导下,选择相对具有代表性的病变部位制作组织芯片。利用组织芯片技术和免疫组化(immunohistochemistry,IHC)SP法检测RASA1在202例NSCLC组织和60例癌旁正常的支气管粘膜组织中的表达情况。RASA1定位于细胞质,胞质阳性染色为黄色、棕黄色或黄褐色。SP法免疫组化检测RASA1蛋白的结果,根据邢等人的判定标准为:随机观察5个高倍镜视野,每个视野计数100个细胞,根据阳性细胞占肿瘤细胞数百分比评分:25%评为1分,25%~50%评为2分,50%评为3分,无阳性细胞评为0分;再结合RASA1在细胞质中的染色强度来评分:浅黄色为1分,棕黄色为2分,黄褐色为3分,无着色细胞为0分。两项得分相乘3分可视为高表达。所有数据的统计学分析均使用SPSS18.0统计软件,采用χ2检验、连续校正卡方检验或者Fisher确切概率法分析各种组织类型中RASA1表达的差异及其与临床病理特征之间的关系。P0.05表示差异具有统计学意义。结果:RASA1在NSCLC组织中的高表达率为74.8%(151/202),在癌旁正常的支气管粘膜组织中的高表达率为93.3%(56/60),RASA1在NSCLC组织中的表达水平显著低于癌旁正常的支气管粘膜组织,差异具有统计学意义(P=0.002)。RASA1在肺腺癌组织中的高表达率为62.7%(64/102),在肺鳞状细胞癌组织中的高表达率为85.6%(77/90),在其他组织类型中的高表达率为100%(10/10),RASA1在肺腺癌组织中表达水平显著低于肺鳞状细胞癌及其他类型的NSCLC组织,差异具有统计学意义(P0.001)。RASA1在男性患者中的高表达率为73.7%(115/156),在女性患者中的高达率为78.3%(36/46),RASA1在男性NSCLC患者中的表达率低于女性患者,但两者之间差异不具有统计学意义(P0.05)。RASA1在淋巴结转移患者中的高表达率为76.5%(65/85),在无淋巴结转移患者中的高表达率为73.5%(86/117),RASA1在淋巴结转移的患者癌组织中的表达率高于无淋巴结转移的患者,但两组间差异不具有统计学意义(P0.05)。根据NSCLC患者临床分期的不同,RASA1在低分期组(Ⅰ/Ⅱ期)的高表达率为75%(123/164),在高分期组(Ⅲ/Ⅳ期)的高表达率为73.3%(28/38),RASA1在低分期组中的表达率高于高分期组,但两组间差异不具有统计学意义(P0.05)。结论:RASA1在NSCLC组织中的表达水平与患者的年龄、性别、淋巴结转移和临床分期均不相关。RASA1基因在NSCLC组织中的表达水平显著低于癌旁正常的支气管粘膜组织,提示RASA1在NSCLC的发生发展中有着重要的作用;RASA1在肺腺癌组织中的表达水平显著低于肺鳞状细胞癌以及其他非腺癌组织,说明RASA1在NSCLC中的表达有着显著地组织学差异性。
[Abstract]:Lung cancer is the most common malignant tumors, and it is also the main cause of death. In recent years, the incidence of lung cancer is still a rising trend in the global scope, in developed countries in Europe and America as well as China's big city, the incidence of lung cancer in male malignant tumor has been ranked first in the incidence of women; also increased rapidly, accounting for common female malignant tumor of the second or third bits, and in patients with lung cancer, non-small cell lung cancer (non-small cell lung cancer, NSCLC) patients accounted for more than 80%, so the research on NSCLC has very important practical significance of.RAS gene mutation is present in about 30% of patients with lung cancer RAS, p21 protein activator 1 (RAS p21 protein activator 1, RASA1) is RAS GTP (RAS GAPs) enzyme activator protein family member to activation of the GTP enzyme, the activation of RAS protein into the non activated state, the termination of signal transduction, Thus inhibition of tumor. The study found that in a variety of human tumors, reduce the expression of RASA1 in different degrees, and the inhibition of lung squamous cell carcinoma and cell proliferation. Objective: To investigate the expression of RASA1 in NSCLC tissues and adjacent normal bronchial mucosa, combined with clinical data, to investigate the RASA1 the expression of NSCLC and tumor size, histological type, correlation between lymph node metastasis and clinical stage and other clinicopathological features and its clinical significance. Methods: during the period from March 2013 to January 2016 by the First Affiliated Hospital of Yangtze University tumor surgery or cardiothoracic surgery resection, pathological diagnosis by 2 surgeons independently diagnosed NSCLC tissue specimens, the clinical inspection data were in accordance with the conditions included 202 pathologic specimens as the experimental group, normal bronchial mucosa in 60 randomly selected cases of paracarcinoma as control group All specimens were obtained after 4% paraformaldehyde perfusion fixed, paraffin embedded storage. By comparing with HE section, under the guidance of doctors in the pathological diagnosis, making the lesion relatively representative tissue microarray. Using tissue microarray technique and immunohistochemistry (immunohistochemistry, IHC) detection method in RASA1 SP 202 cases of NSCLC tissues and 60 cases of adjacent normal bronchial mucosa.RASA1 localized in the cytoplasm, cytoplasmic staining is yellow, brown yellow or brown.SP immunohistochemical detection of RASA1 protein results according to the criteria for Xing et al: random observation of 5 high magnification, each according to the View Count of 100 cells, positive cells accounted for the percentage of tumor cells score: 25% rated 1 points, 25%~50% awarded 2 points, 50% points ranked 3, no positive cells were graded 0; combined with the staining intensity of RASA1 in the cytoplasm. To score 1 points: light yellow, yellow brown for 2 minutes, 3 points, 0 points. No staining in cell multiplication of 3 two scores can be regarded as a high expression. All the data were statistically analyzed using SPSS18.0 statistical software, using 2 test, continuous correction chi square test or Fisher exact probability analysis of expression of RASA1.P0.05 in various tissue types and their relationship with clinicopathological features that the difference was statistically significant. Results: the high expression of RASA1 in NSCLC tissues was 74.8% (151/202), in the adjacent tissue of bronchial mucosa in normal rate was 93.3% (56/60), the expression level of RASA1 in the NSCLC tissue were significantly lower than that in normal bronchial mucosa adjacent to the cancer, the difference was statistically significant (P=0.002) high expression of.RASA1 in lung adenocarcinoma tissues was 62.7% (64/102), high expression in lung squamous cell carcinoma tissues was 85.6 % (77/90), high expression in other tissue types in the rate of 100% (10/10), the expression of RASA1 in lung cancer tissues was significantly lower than that of lung squamous cell carcinoma and other types of NSCLC, the difference was statistically significant (P0.001) high expression of.RASA1 in male patients was 73.7% (115/156). The high rate in female patients was 78.3% (36/46), the expression of RASA1 in male patients with NSCLC was lower than female patients, but the difference was not statistically significant (P0.05).RASA1 in lymph node metastasis in patients with high expression rate was 76.5% (65/ 85), the high expression in patients with lymph node metastasis the rate was 73.5% (86/117), RASA1 expression in lymph node metastasis in patients with carcinoma without lymph node metastasis was higher than that of patients, but the difference between the two groups was not statistically significant (P0.05). According to the clinical NSCLC staging in patients with different RASA1 in the lower stage group (I / II) The high expression rate of 75% (123/164), in the high stage group (stage III / IV) high expression rate was 73.3% (28/38), the expression of RASA1 in the low stage in the group was higher than that of high score group, but the difference between the two groups was not statistically significant (P0.05). Conclusion: the expression level of patients with RASA1 in the NSCLC organization of the age, gender, expression level of lymph node metastasis and clinical stage were not related to.RASA1 gene in NSCLC tissues was significantly lower than that in normal bronchial mucosa adjacent to carcinoma, suggesting that RASA1 plays an important role in the occurrence and development of NSCLC; RASA1 in lung adenocarcinoma tissues significantly lower lung squamous cell carcinoma and other non adenocarcinoma, the expression of RASA1 in NSCLC has a significant histological differences.

【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

【相似文献】