【摘要】：研究背景:胃癌在全世界很多地方的發(fā)病率都很高。在我國,胃癌依然是常見的胃腸道腫瘤之一,平均每年新發(fā)病例約40萬例左右,占全球總發(fā)病例數(shù)的42%[1]。據(jù)全球腫瘤研究機構(International Agency for research on cancer)官方網站公布的全球腫瘤發(fā)病率和死亡率結果,在2002年,男性年齡調整的胃癌的發(fā)病率為22.0/10萬人口,女性為10.4/10萬人口;男性胃癌的死亡率為16.3/10萬人口,女性胃癌的死亡率為7.9/10萬人口。在男性常見腫瘤中,胃癌位居第3位,僅次于肺癌和前列腺癌,死亡率在僅次于肺癌;胃癌是女性常見腫瘤中的第5位,死亡率也高居第4位[2]。而依據(jù)2015年中國惡性腫瘤發(fā)病率和死亡分析顯示:胃癌在全國男性惡性腫瘤發(fā)病率中攀升至第2位,僅位于肺癌之后。在女性胃腸道惡性腫瘤發(fā)病率中上升至第4位。而現(xiàn)在胃癌的主要治療方法為手術以及術后放化療,然而大多患者在確診胃癌時已為胃癌晚期,失去了手術機會,姑息性放化療效果也不理想。所以目前這些治療手段并不能完全緩解病人的痛苦,更加達不到治愈了疾病的目標[3]。近幾年,研究領域出現(xiàn)一個熱點問題-應用細胞自噬治療惡性腫瘤。自噬相關蛋白Beclin1和LC3是兩種存在于哺乳動物內的自噬蛋白,在自噬作用中起到抑制腫瘤發(fā)生發(fā)展的作用。所以進一步探索胃癌的分子生物學特性,發(fā)現(xiàn)新型腫瘤分子標志物,并且研究其和胃癌臨床病理因素的聯(lián)系,明確自噬在胃癌發(fā)生和發(fā)展過程中的可能作用,為臨床上緩解胃癌患者的病情起到了重要作用。自噬(autophagy):細胞自噬是指機體細胞在各種不利因素刺激下以自身溶酶體分解降解胞內的蛋白質、核糖體、大分子物質及受損細胞器的過程,并重新利用被分解的物質再次維護細胞的內環(huán)境穩(wěn)定。目前自噬與胃癌發(fā)生發(fā)展的關系尚不明確,自噬基因Beclin1和LC3是否相互作用共同促進胃癌的發(fā)生發(fā)展,是近年研究的重要問題,對于胃癌的診治判斷、指導治療和療效預后有非常重要的意義。研究目的:分析自噬相關基因Beclin1和LC3在同一患者胃癌、癌旁組織和正常胃組織中的表達差異;研究Beclin1、LC3的表達與胃癌臨床病理特征的關系,從而了解自噬會不會影響胃癌的發(fā)生或發(fā)展。研究方法:應用即用型免疫組化法觀察檢測自噬蛋白Beclin1和LC3在胃癌、胃的癌旁組織和正常胃組織分別60例中的表達狀況;應用spearman檢驗分析胃癌Beclin1及LC3的表達有沒有相關性;應用χ2檢驗分析Beclin1、LC3的表達與胃癌患者的臨床病理學參數(shù)。研究結果:1.Beclin1在胃癌和癌旁組織以及正常組織中的陽性表達率分別為28.3%(17/60)、47.7%(28/60)、61.7%(37/60);LC3在胃癌和癌旁組織以及正常組織中的陽性表達率分別為31.7%(19/60)、53.3%(32/60)、68.3%(41/60);Beclin1和LC3在胃癌和癌旁組織中的陽性表達率顯著低于正常組織(p0.05).2.Beclin1和LC3在胃癌組織中的表達呈顯著正相關(r=0.445,p0.05)。3.Beclin1、LC3的表達與胃癌患者年齡、性別、腫瘤位置均無顯著相關性(p0.05)。結論:1.自噬相關蛋白Beclin1和LC3在胃癌組織中的表達明顯降低;2.Beclin1、LC3的表達與胃癌患者年齡、性別、腫瘤位置無顯著相關性;而與腫瘤分期、分化程度和淋巴結轉移有明顯相關性。3.Beclin1和LC3的陽性表達與胃癌的臨床分期晚和胃癌淋巴結轉移呈正相關。
[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.
【學位授予單位】：延安大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.2

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