本文選題：黑素瘤缺乏因子2　切入點：結(jié)直腸癌　出處：《西南醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:黑素瘤缺乏因子2(absent in melanoma 2,AIM2)是近年來研究發(fā)現(xiàn)的一種存在于細胞質(zhì)中的雙鏈DNA感受器,能夠通過形成炎性復合體的方式誘導炎性反應(yīng)以及固有免疫應(yīng)答,且與惡性腫瘤的發(fā)生發(fā)展密切相關(guān)。AIM2在惡性腫瘤的組織中存在一定程度的異常表達,其表達強度可能與惡性腫瘤患者的臨床病理特征以及預后有關(guān),但其參與腫瘤發(fā)生的方式和機制尚不明確,且國內(nèi)也無相關(guān)數(shù)據(jù)。本研究收集可手術(shù)切除的結(jié)直腸癌患者,以免疫組化方法了解結(jié)直腸癌患者腫瘤組織中AIM2基因的表達水平,并分析其與結(jié)直腸癌患者臨床病理資料之間的關(guān)系。方法:于2016年1月至6月收集手術(shù)切除的結(jié)直腸癌患者的腫瘤標本。并取腫瘤組織及鄰近正常組織各一處,行AIM2免疫組化染色,鏡下仔細觀察AIM2在結(jié)直腸癌組織和鄰近正常組織中的表達情況,并登記結(jié)直腸癌患者完善的病理資料,進而分析AIM2的表達與結(jié)直腸癌患者病理資料之間是否存在相關(guān)性。本實驗采用酶標聚合物法(Labelled dextran polymer,LDP),先將辣根過氧化物標記在葡聚糖聚合物上,然后再與第二抗體鏈接形成Envision二抗,AIM2特異性一抗與組織細胞抗原結(jié)合后,利用Envision二抗與抗原抗體復合物中的AIM2一抗相結(jié)合,通過Envision二抗上的酶參與顯色反應(yīng),進而顯示AIM2在結(jié)直腸癌組織及鄰近正常組織中的表達情況。結(jié)果:2016年1月至6月共納入100例完成手術(shù)的結(jié)直腸癌患者的臨床及病理資料,其中男性患者63例,女性患者37例,平均年齡62.88±10.56歲。免疫組化染色發(fā)現(xiàn)AIM2蛋白陽性表達部位主要集中在腸上皮細胞的細胞質(zhì)中。1、100例結(jié)直腸癌患者的腫瘤組織和鄰近正常組織中,AIM2的表達陽性例數(shù)分別為42列(42%)和85例(85%)。提示AIM2在結(jié)直腸癌組織中的表達明顯低于鄰近正常組織,差異有統(tǒng)計學意義(χ2=39.888,P0.05);2、與陽性表達者相比,結(jié)直腸癌患者腫瘤組織中AIM2表達陰性的患者,具有更差的T分期(腫瘤浸潤深度)、N分期(淋巴結(jié)轉(zhuǎn)移)以及腫瘤分期,且更容易出現(xiàn)錯配修復蛋白表達陰性(dMMR)(χ2=4.408、4.995、6.565、3.923;P0.05);而AIM2表達水平在不同性別、年齡、腫瘤部位、腫瘤直徑、腫瘤分化程度以及腫瘤病理學類型分組中差異無統(tǒng)計學意義(χ2=0.375、0.642、0.270、0.037、1.002、1.376;P0.05).結(jié)論:1、AIM2基因表達的蛋白主要位于結(jié)直腸上皮細胞的細胞質(zhì)中;2、結(jié)直腸癌組織中AIM2表達明顯低于鄰近正常組織,提示AIM2可能是一種潛在的腫瘤抑制因子,而AIM2的低表達或缺失可能是促進結(jié)直腸癌發(fā)生發(fā)展的一個重要原因;3、腫瘤組織中AIM2低表達的結(jié)直腸癌患者,具有更差的病理分期,提示預后可能更差。4、腫瘤組織中AIM2低表達的結(jié)直腸癌患者,dMMR發(fā)生率更高,提示AIM2表達的降低或缺失,有可能是錯配修復蛋白缺失所致基因突變的后果。
[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 鹵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.
【學位授予單位】：西南醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.34

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