自噬相关蛋白Beclin1、LC3在胃癌组织的表达及其临床意义

发布时间：2019-06-03 05:37

【摘要】：研究背景:胃癌在全世界很多地方的发病率都很高。在我国,胃癌依然是常见的胃肠道肿瘤之一,平均每年新发病例约40万例左右,占全球总发病例数的42%[1]。据全球肿瘤研究机构(International Agency for research on cancer)官方网站公布的全球肿瘤发病率和死亡率结果,在2002年,男性年龄调整的胃癌的发病率为22.0/10万人口,女性为10.4/10万人口;男性胃癌的死亡率为16.3/10万人口,女性胃癌的死亡率为7.9/10万人口。在男性常见肿瘤中,胃癌位居第3位,仅次于肺癌和前列腺癌,死亡率在仅次于肺癌;胃癌是女性常见肿瘤中的第5位,死亡率也高居第4位[2]。而依据2015年中国恶性肿瘤发病率和死亡分析显示:胃癌在全国男性恶性肿瘤发病率中攀升至第2位,仅位于肺癌之后。在女性胃肠道恶性肿瘤发病率中上升至第4位。而现在胃癌的主要治疗方法为手术以及术后放化疗,然而大多患者在确诊胃癌时已为胃癌晚期,失去了手术机会,姑息性放化疗效果也不理想。所以目前这些治疗手段并不能完全缓解病人的痛苦,更加达不到治愈了疾病的目标[3]。近几年,研究领域出现一个热点问题-应用细胞自噬治疗恶性肿瘤。自噬相关蛋白Beclin1和LC3是两种存在于哺乳动物内的自噬蛋白,在自噬作用中起到抑制肿瘤发生发展的作用。所以进一步探索胃癌的分子生物学特性,发现新型肿瘤分子标志物,并且研究其和胃癌临床病理因素的联系,明确自噬在胃癌发生和发展过程中的可能作用,为临床上缓解胃癌患者的病情起到了重要作用。自噬(autophagy):细胞自噬是指机体细胞在各种不利因素刺激下以自身溶酶体分解降解胞内的蛋白质、核糖体、大分子物质及受损细胞器的过程,并重新利用被分解的物质再次维护细胞的内环境稳定。目前自噬与胃癌发生发展的关系尚不明确,自噬基因Beclin1和LC3是否相互作用共同促进胃癌的发生发展,是近年研究的重要问题,对于胃癌的诊治判断、指导治疗和疗效预后有非常重要的意义。研究目的:分析自噬相关基因Beclin1和LC3在同一患者胃癌、癌旁组织和正常胃组织中的表达差异;研究Beclin1、LC3的表达与胃癌临床病理特征的关系,从而了解自噬会不会影响胃癌的发生或发展。研究方法:应用即用型免疫组化法观察检测自噬蛋白Beclin1和LC3在胃癌、胃的癌旁组织和正常胃组织分别60例中的表达状况;应用spearman检验分析胃癌Beclin1及LC3的表达有没有相关性;应用χ2检验分析Beclin1、LC3的表达与胃癌患者的临床病理学参数。研究结果:1.Beclin1在胃癌和癌旁组织以及正常组织中的阳性表达率分别为28.3%(17/60)、47.7%(28/60)、61.7%(37/60);LC3在胃癌和癌旁组织以及正常组织中的阳性表达率分别为31.7%(19/60)、53.3%(32/60)、68.3%(41/60);Beclin1和LC3在胃癌和癌旁组织中的阳性表达率显著低于正常组织(p0.05).2.Beclin1和LC3在胃癌组织中的表达呈显著正相关(r=0.445,p0.05)。3.Beclin1、LC3的表达与胃癌患者年龄、性别、肿瘤位置均无显著相关性(p0.05)。结论:1.自噬相关蛋白Beclin1和LC3在胃癌组织中的表达明显降低;2.Beclin1、LC3的表达与胃癌患者年龄、性别、肿瘤位置无显著相关性;而与肿瘤分期、分化程度和淋巴结转移有明显相关性。3.Beclin1和LC3的阳性表达与胃癌的临床分期晚和胃癌淋巴结转移呈正相关。
[Abstract]:Background: The incidence of gastric cancer in many parts of the world is high. In China, gastric cancer is one of the most common gastrointestinal tumors, with an average of about 400,000 new cases per year, accounting for 42% of the total number of patients in the world[1]. In 2002, the incidence of male-age-adjusted gastric cancer was 22.0 per 100,000 in 2002 and 10.4 per 100,000 in women, according to the results of global tumor morbidity and mortality, published by the International Agency for Research on Cancer, and the death rate for male gastric cancer was 16.3 per 100,000, The mortality rate for female gastric cancer was 7.9 per 100,000. In male common tumors, gastric cancer is the third, only after lung cancer and prostate cancer, and the mortality rate is second only to lung cancer; gastric cancer is the fifth of the female common tumors, and the mortality rate is high in the fourth[2]. According to the analysis of the incidence and death of malignant tumor in China in 2015, the incidence of gastric cancer has climbed to the second place in the incidence of malignant tumor in the whole country, only after lung cancer. In the incidence of the malignant tumor of the female gastrointestinal tract, the incidence of malignant tumor was increased to the 4th. However, most of the patients who have been diagnosed with gastric cancer have been diagnosed with advanced gastric cancer, have lost the opportunity of operation, and the effect of palliative radiotherapy and chemotherapy is not ideal. So at present, these treatments do not complete complete remission of the patient's pain, and can't achieve the target[3] of the disease. In recent years, there has been a hot issue in the field of research-the application of cell autophagy in the treatment of malignant tumors. The autophagy-related proteins, Beclin1 and LC3, are two autophagy proteins that are present in mammals and play a role in inhibiting the development of tumorigenesis in autophagy. Therefore, the molecular biological characteristics of the gastric cancer are further explored, the novel tumor molecular markers are found, and the relationship between the clinicopathological factors of the gastric cancer and the gastric cancer is studied, and the possible role of autophagy in the occurrence and development of the gastric cancer is clarified, so that the clinical remission of the gastric cancer patients plays an important role. Autophagy (autophagy): the autophagy of the cell is the process of decomposing the protein, the ribosome, the macromolecular substance and the damaged organelle in the cell under various adverse factors, and re-maintaining the internal environment of the cell with the decomposed substance. At present, the relationship between autophagy and the development of gastric cancer is not clear, and whether the autophagy gene Beclin1 and LC3 interact to promote the development of gastric cancer is an important problem in recent years. It is of great significance to the diagnosis and treatment of gastric cancer, to guide the treatment and the prognosis of the curative effect. Objective: To study the expression of self-autophagy-related gene Beclin1 and LC3 in gastric cancer, adjacent tissue and normal gastric tissue of the same patient, and to study the relationship between the expression of Bechin1 and LC3 and the clinicopathological characteristics of gastric cancer, so as to understand that autophagy does not affect the occurrence or development of gastric cancer. Methods: The expression of Bechlin 1 and LC3 in 60 cases of gastric cancer, gastric cancer and normal gastric tissues were detected by using the immunohistochemical method. The expression of Bechin1 and LC3 in gastric cancer was analyzed by using the spearman test. The expression of LC3 and the clinicopathological parameters of gastric cancer patients. Results of the study: 1. The positive expression rates of Bechin1 in gastric and non-adjacent tissues and normal tissues were 28.3% (17/60), 47.7% (28/60) and 61.7% (37/60), respectively. The positive expression rates of LC3 in gastric and non-adjacent tissues and normal tissues were 31.7% (19/60), 53.3% (32/60) and 68.3% (41/60) respectively. The positive expression rate of Bechin1 and LC3 in gastric cancer and adjacent tissues was significantly lower than that of normal tissues (p0.05). (r = 0.445, p0.05).3. The expression of Bechin1 and LC3 had no significant correlation with the age, sex and tumor location of gastric cancer (p0.05). Conclusion:1. The expression of Bechin1 and LC3 of autophagy in gastric cancer was significantly decreased;2. The expression of Bechin1 and LC3 had no significant correlation with the age, sex and tumor location of gastric cancer. 3. The positive expression of Bechin1 and LC3 was positively correlated with the clinical stage of gastric cancer and the lymph node metastasis of gastric cancer.
【学位授予单位】：延安大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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