结直肠癌手术患者肿瘤组织中AIM2表达情况及其与临床病理资料的相关性研究

发布时间：2018-03-10 04:29

本文选题：黑素瘤缺乏因子2　切入点：结直肠癌　出处：《西南医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:黑素瘤缺乏因子2(absent in melanoma 2,AIM2)是近年来研究发现的一种存在于细胞质中的双链DNA感受器,能够通过形成炎性复合体的方式诱导炎性反应以及固有免疫应答,且与恶性肿瘤的发生发展密切相关。AIM2在恶性肿瘤的组织中存在一定程度的异常表达,其表达强度可能与恶性肿瘤患者的临床病理特征以及预后有关,但其参与肿瘤发生的方式和机制尚不明确,且国内也无相关数据。本研究收集可手术切除的结直肠癌患者,以免疫组化方法了解结直肠癌患者肿瘤组织中AIM2基因的表达水平,并分析其与结直肠癌患者临床病理资料之间的关系。方法:于2016年1月至6月收集手术切除的结直肠癌患者的肿瘤标本。并取肿瘤组织及邻近正常组织各一处,行AIM2免疫组化染色,镜下仔细观察AIM2在结直肠癌组织和邻近正常组织中的表达情况,并登记结直肠癌患者完善的病理资料,进而分析AIM2的表达与结直肠癌患者病理资料之间是否存在相关性。本实验采用酶标聚合物法(Labelled dextran polymer,LDP),先将辣根过氧化物标记在葡聚糖聚合物上,然后再与第二抗体链接形成Envision二抗,AIM2特异性一抗与组织细胞抗原结合后,利用Envision二抗与抗原抗体复合物中的AIM2一抗相结合,通过Envision二抗上的酶参与显色反应,进而显示AIM2在结直肠癌组织及邻近正常组织中的表达情况。结果:2016年1月至6月共纳入100例完成手术的结直肠癌患者的临床及病理资料,其中男性患者63例,女性患者37例,平均年龄62.88±10.56岁。免疫组化染色发现AIM2蛋白阳性表达部位主要集中在肠上皮细胞的细胞质中。1、100例结直肠癌患者的肿瘤组织和邻近正常组织中,AIM2的表达阳性例数分别为42列(42%)和85例(85%)。提示AIM2在结直肠癌组织中的表达明显低于邻近正常组织,差异有统计学意义(χ2=39.888,P0.05);2、与阳性表达者相比,结直肠癌患者肿瘤组织中AIM2表达阴性的患者,具有更差的T分期(肿瘤浸润深度)、N分期(淋巴结转移)以及肿瘤分期,且更容易出现错配修复蛋白表达阴性(dMMR)(χ2=4.408、4.995、6.565、3.923;P0.05);而AIM2表达水平在不同性别、年龄、肿瘤部位、肿瘤直径、肿瘤分化程度以及肿瘤病理学类型分组中差异无统计学意义(χ2=0.375、0.642、0.270、0.037、1.002、1.376;P0.05).结论:1、AIM2基因表达的蛋白主要位于结直肠上皮细胞的细胞质中;2、结直肠癌组织中AIM2表达明显低于邻近正常组织,提示AIM2可能是一种潜在的肿瘤抑制因子,而AIM2的低表达或缺失可能是促进结直肠癌发生发展的一个重要原因;3、肿瘤组织中AIM2低表达的结直肠癌患者,具有更差的病理分期,提示预后可能更差。4、肿瘤组织中AIM2低表达的结直肠癌患者,dMMR发生率更高,提示AIM2表达的降低或缺失,有可能是错配修复蛋白缺失所致基因突变的后果。
[Abstract]:Objective: melanoma deficiency factor 2absent in melanoma 2 (AIM2) is a double-stranded DNA receptor found in cytoplasm in recent years, which can induce inflammatory response and innate immune response by forming inflammatory complex. The expression of AIM2 may be related to the clinicopathological features and prognosis of malignant tumors. However, the way and mechanism of its involvement in tumorigenesis is not clear, and there are no relevant data in China. In this study, we collected patients with resectable colorectal cancer and studied the expression level of AIM2 gene in colorectal cancer tissues by immunohistochemical method. Methods: from January 2016 to June, the tumor specimens of patients with colorectal cancer were collected, and the tumor tissues and adjacent normal tissues were taken. AIM2 immunohistochemical staining was used to observe the expression of AIM2 in colorectal cancer tissues and adjacent normal tissues under microscope, and to register the complete pathological data of patients with colorectal cancer. The expression of AIM2 was correlated with the pathological data of colorectal cancer patients. In this experiment, the horseradish peroxide was labeled on the dextran polymer by enzyme-labeled polymer method. Then the second antibody was linked to the second antibody to form a specific first antibody of Envision second antibody to the tissue cell antigen, then the second antibody of Envision was combined with the first antibody of the AIM2 antibody complex, and the enzyme on the second antibody of Envision was used to participate in the chromogenic reaction. Results: from January 2016 to June, the clinical and pathological data of 100 patients with colorectal cancer were included, including 63 male patients and 37 female patients. The average age was 62.88 卤10.56 years old. Immunohistochemical staining showed that the positive expression of AIM2 protein was mainly located in the cytoplasm of intestinal epithelial cells. The expression of AIM2 in colorectal cancer tissues was significantly lower than that in adjacent normal tissues. The difference was statistically significant (蠂 ~ 2 / 39.888 / P0.05 / 2). The patients with negative AIM2 expression in colorectal cancer had worse T stage (depth of tumor invasion) (lymph node metastasis) and tumor stage than those with positive expression. The expression of mismatch repair protein was more likely to be negative (蠂 ~ 2 ~ 2 ~ (4.408) ~ 4.995 ~ (6.565)) ~ (3.923) P _ (0.05), while the expression level of AIM2 was found in different sex, age, tumor location, tumor diameter, and so on. There was no significant difference in differentiation degree and pathological type of tumor (蠂 ~ 2 ~ 2 ~ (0.375) ~ (0.64) ~ (2)) ~ (0.270) ~ (0.37) ~ (1.002) ~ (1.376) ~ (-1) AIM2 gene expression in the cytoplasm of colorectal epithelial cells, and the expression of AIM2 in colorectal cancer was significantly lower than that in adjacent normal tissues. The results suggest that AIM2 may be a potential tumor suppressor, and the low expression or absence of AIM2 may be an important reason for the development of colorectal cancer. Patients with low expression of AIM2 in tumor tissues have worse pathological stages. The results suggest that the prognosis may be worse, and the incidence of AIM2 low expression in colorectal cancer patients is higher, suggesting that the decrease or deletion of AIM2 expression may be the result of gene mutation caused by mismatch repair protein deletion.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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