ARID1A蛋白表达与胃癌临床病理特征相关性的研究

发布时间：2018-06-23 22:18

本文选题：Arid1a + BAF250a　；参考：《皖南医学院》2017年硕士论文

【摘要】：目的:研究Arid1a蛋白表达情况与胃癌发病及其肿瘤病理特征之间的关系。方法:选取皖南医学院第一附属弋矶山医院2012年至2015年之间行胃癌根治术以及胃良性病变大部切除术的患者,排除胃原位癌及远处器官转移患者。对胃癌标本(含癌旁组织)以及正常胃粘膜的组织蜡块切片后进行免疫组化染色(一抗为兔抗人单克隆Arid1a抗体,克隆号EPR13501)。在两位病理医师指导下对每张切片进行结果判定。收集患者的一般资料、既往病史以及肿瘤病理特征等资料;最后运用统计学方法对结果进行分析。结果:本次研究共完成正常胃黏膜免疫组化染色42例以及胃癌组织免疫组化染色104例,其中包含癌旁组织的免疫组化染色切片75例。Arid1a蛋白在正常胃黏膜、癌旁组织以及胃癌组织中的表达缺失率分别4.76%(2/42)、8.00%(6/75)、23.08%(24/104);Arid1a蛋白在胃癌组织中表达缺失率最高,且差异存在统计学意义(正常胃黏膜vs胃癌组织,P=0.008;癌旁组织vs胃癌组织,P=0.008)。Arid1a蛋白在胃癌患者中的表达缺失率与性别、年龄、是否吸烟以及饮酒之间均无明显相关性(均P0.05)。但与既往有胃溃疡病史有关,且差异有统计学意义(P=0.048)。通过分析发现,Arid1a蛋白表达缺失率与肿瘤位置,Lauren分型,分化程度以及是否有神经侵犯之间无相关性(均P0.05)。在肿瘤浸润深度方面,实验结果显示T3+T4期胃癌病例占63.46%(66/104);肿瘤浸润越深(T分期),其Arid1a蛋白表达缺失率越高。Arid1a蛋白表达缺失率在T3、T4期胃癌患者中分别为30.00%(9/30)、33.33%(12/36);明显高于T1期(6.67%,1/15)及T2期(8.70%,2/23),差别存在统计学意义(P=0.048)。同时发现淋巴结转移越多,胃癌组织中Arid1a蛋白表达缺失率也越高,其中N2、N3胃癌组织中Arid1a蛋白表达缺失率分别为31.82%(7/22)和41.38%(12/29),明显高于N0(6.90%)及N1(12.50%)的Arid1a蛋白表达缺失率,且差别存在统计学意义(P=0.007)。在伴有脉管侵犯的胃癌患者中,其Arid1a蛋白表达缺失率明显高于无脉管侵犯的胃癌患者,差别有统计学意义(37.50%vs14.06%,P=0.008)。肿瘤直径大于5cm的胃癌患者中Arid1a蛋白表达缺失率最高,达42.42%(13/41),明显高于肿瘤小于等于3cm(5.88%)和大于3小于等于5cm(21.62%)的胃癌患者,差别有统计学意义(P=0.002)。结论:既往有胃溃疡病史的胃癌患者Arid1a蛋白表达缺失率高,提示Arid1a蛋白表达缺失与胃溃疡有关。Arid1a蛋白表达缺失与胃癌肿瘤大小、浸润深度、淋巴结转移及脉管侵犯等肿瘤特征有关;提示Arid1a蛋白表达缺失的胃癌患者具有较差的肿瘤生物学行为。Arid1a蛋白表达缺失与胃癌的发病有关,提示Arid1a基因可能是一种抑癌基因。
[Abstract]:Objective: to study the relationship between the expression of Arid1a protein and the pathogenesis and pathological features of gastric cancer. Methods: patients who underwent radical gastrectomy and subtotal resection of benign gastric lesions between 2012 and 2015 were selected to exclude patients with gastric carcinoma in situ and distant organ metastasis. The specimens of gastric cancer (including paracancerous tissue) and normal gastric mucosa were stained with immunohistochemical staining (rabbit monoclonal Arid1a antibody, clone EPR13501). The results of each section were determined under the guidance of two pathologists. Collect the general data of the patients, past medical history and tumor pathological characteristics. Finally, the results were analyzed by statistical method. Results: in this study, 42 cases of normal gastric mucosa and 104 cases of gastric cancer tissues were stained with immunohistochemical staining, including 75 cases of immunohistochemical sections of paracancerous tissues. Arid1a protein was found in normal gastric mucosa. The deletion rate of Arid1a protein in paracancerous tissues and gastric cancer tissues was 4.76% (2 / 42) and 8.00% (6 / 75) or 23.08% (24 / 104), respectively. There was no significant correlation between the deletion rate of Arid1a protein and sex, age, smoking or alcohol consumption in gastric cancer patients (normal gastric mucosa vs gastric cancer tissue P0. 008; paracancerous tissue vs gastric cancer tissue P0. 008). But it was related to the history of gastric ulcer, and the difference was statistically significant (P0. 048). It was found that there was no correlation between the deletion rate of Arid1a protein and the Lauren type of tumor location, the degree of differentiation and the presence of neural invasion (P0.05). In terms of the depth of tumor infiltration, The results showed that 63.46% (66 / 104) of patients with T3T4 gastric cancer, and 63.46% (66 / 104) of patients with T3T4 gastric cancer, the higher the loss rate of Arid1a protein expression was, the higher the deletion rate of Arid1a protein expression was in T3T4 stage gastric cancer patients (30.00% (9/ 30) 33.33% (12 / 36), respectively), which was significantly higher than that in T1 stage (6.67115) and T2 stage (8.70% / 23). The difference was statistically significant (P0. 048). It was also found that the higher the lymph node metastasis, the higher the deletion rate of Arid1a protein in gastric cancer tissue. The deletion rate of Arid1a protein in N2N3 gastric cancer was 31.82% (7 / 22) and 41.38% (12 / 29) respectively, which was significantly higher than that of N0 (6.90%) and N1 (12.50%). The difference was statistically significant (P0. 007). The loss rate of Arid1a protein expression in patients with vascular invasion was significantly higher than that in patients without vessel invasion (37.50 vs 14.06). The deletion rate of Arid1a protein in patients with tumor diameter larger than 5cm was 42.42% (13 / 41), which was significantly higher than that in patients with tumor less than or equal to 3cm (5.88%) and greater than 3 (less than 3 equal to 5cm (21.62%) (P < 0.002). Conclusion: the deletion rate of Arid1a protein in gastric cancer patients with a history of gastric ulcer is high, suggesting that the loss of Arid1a protein expression is related to gastric ulcer and the tumor size and depth of invasion. Lymph node metastasis and vascular invasion were related to the tumor characteristics, suggesting that the loss of Arid1a protein expression in gastric cancer patients had poor tumor biological behavior. The loss of Arid1a protein expression was associated with the pathogenesis of gastric cancer, suggesting that the Arid1a gene might be a tumor suppressor gene.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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