【摘要】：背景和目的:胃癌是常見的惡性腫瘤之一,它的早期診斷率低、治療效果不理想,盡管其發(fā)病率在世界范圍內(nèi)有所下降,但在我國(guó)胃癌的發(fā)病率和死亡率仍居惡性腫瘤的前三位,因此盡早診斷,綜合治療是治療胃癌的關(guān)鍵。近年來(lái),隨著基因靶向治療理念的出現(xiàn),在分子水平上探討胃癌相關(guān)基因在組織和血液中的表達(dá)模式,將有助于胃癌的早期診斷,評(píng)估預(yù)后,從而改善胃癌的治療效果。miRNA是一種廣泛存在于生物體內(nèi)的非編碼單鏈小分子RNA,研究證實(shí),miRNAs在腫瘤的組織和外周血中存在異常表達(dá),參與調(diào)控腫瘤相關(guān)基因,影響腫瘤的發(fā)生、發(fā)展、侵襲、增殖、凋亡和轉(zhuǎn)移,在不同的臨床分期、不同分化程度和預(yù)后方面存在動(dòng)態(tài)變化,為腫瘤的早期診斷提供了理論基礎(chǔ)。然而miR-126、miR-199a在胃癌的發(fā)生、發(fā)展過(guò)程中表達(dá)的機(jī)制尚不十分清楚。本文旨在探討miR-126、miR-199a在胃癌組織與血清中的表達(dá)與臨床病理特征之間的關(guān)系,分析血清miR-126、miR-199a的診斷價(jià)值,為miRNAs作為診斷胃癌的生物學(xué)標(biāo)志物、判斷病情以及發(fā)病機(jī)制的研究提供依據(jù)。方法:收集南通大學(xué)附屬第二醫(yī)院于2016年06月至2016年12月住院期間胃腸外科收治的術(shù)前病理診斷明確的胃癌患者42例作為實(shí)驗(yàn)組。收集南通大學(xué)附屬醫(yī)院體檢中心體檢的年齡相仿的60例健康人群作為對(duì)照組。標(biāo)本系胃癌根治術(shù)后新鮮標(biāo)本,于手術(shù)后30 min內(nèi)取其癌組織及遠(yuǎn)癌對(duì)照組織(距離癌組織5 cm以上)作快速冰凍以證實(shí)為胃癌,取下的組織放液氮中凍存?zhèn)溆�。采集患者術(shù)前、術(shù)后1周的外周血各5 mL,采集健康對(duì)照組人群的外周血5 mL,采用實(shí)時(shí)定量PCR的方法檢測(cè)miR-126、miR-199a在組織和血清中的表達(dá)情況。于術(shù)前和術(shù)后1周左右分別采集患者外周血5 mL送檢驗(yàn)科作標(biāo)準(zhǔn)化癌胚抗原(CEA)檢測(cè),參考值為0～10ng/L。結(jié)果:1、在胃癌組織中,miR-126在癌組織中的相對(duì)表達(dá)水平(7.17±2.62)(t=7.276,P0.05),兩組存在統(tǒng)計(jì)學(xué)差異;miR-126在癌組織中的表達(dá)與腫瘤大小、臨床分期、組織分化程度有關(guān);miR-199a在癌組織中的相對(duì)表達(dá)水平(12.04±2.27)高于遠(yuǎn)癌對(duì)照者(2.12±1.11)(t=3.908,P0.05),兩組存在統(tǒng)計(jì)學(xué)差異;miR-199a在癌組織中的表達(dá)與腫瘤臨床分期、浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移有關(guān)。2、在胃癌患者血清中,miR-126在術(shù)前血清的相對(duì)表達(dá)水平(2.49±3.36)低于術(shù)后(7.83±2.61)(t=6.316,P0.05);在術(shù)后血清中的相對(duì)表達(dá)水平低于健康對(duì)照者(9.60±4.01)(t=4.338,P0.05),兩組存在統(tǒng)計(jì)學(xué)差異;miR-126在血清中的表達(dá)與腫瘤臨床分期、組織分化程度有關(guān);miR-199a在術(shù)前血清中的相對(duì)表達(dá)水平(30.04±5.04)高于術(shù)后(14.03±6.02)(t=6.778,P0.05);在術(shù)后血清中的相對(duì)表達(dá)水平高于健康對(duì)照者(5.81±4.67)(t=7.684,P0.05),兩組存在統(tǒng)計(jì)學(xué)差異;miR-199a在血清中的表達(dá)與腫瘤臨床分期、浸潤(rùn)深度有關(guān)。3、胃癌組織miR-126的診斷效率ROC曲線下面積AUC為0.823,血清AUC為0.776;胃癌組織miR-199a的診斷效率ROC曲線下面積AUC為0.862,血清AUC為0.918;CEA的診斷效率ROC曲線下面積AUC為0.537。4、Pearson相關(guān)分析顯示,胃癌患者癌組織與術(shù)前血清中miR-126的相對(duì)表達(dá)水平呈正相關(guān)(r=0.484,P0.01);癌組織與術(shù)前血清中miR-199a的表達(dá)水平呈正相關(guān)(r=0.65,P0.01)。結(jié)論:1、胃癌組織和血清miR-126表達(dá)下調(diào)、miR-199a表達(dá)上調(diào),兩者均與胃癌的發(fā)生發(fā)展相關(guān)。2、胃癌患者血清miR-126的表達(dá)水平與臨床分期和組織分化程度有關(guān),miR-199a的表達(dá)水平與腫瘤浸潤(rùn)深度和臨床分期有關(guān)。血清miR-126、miR-199a的表達(dá),可以作為評(píng)估胃癌患者病情嚴(yán)重程度的標(biāo)志之一。3、血清miR-126、miR-199a的表達(dá)對(duì)胃癌具有較好的診斷價(jià)值,兩者均優(yōu)于血清CEA;組織和血清miR-126、miR-199a的表達(dá)水平呈正相關(guān),有望成為有價(jià)值的診斷胃癌的生物學(xué)標(biāo)志物。
[Abstract]:BACKGROUND AND OBJECTIVE: Gastric cancer is one of the common malignant tumors. Its early diagnosis rate is low and the therapeutic effect is not ideal. Although the incidence of gastric cancer has declined worldwide, the incidence and mortality of gastric cancer still rank the top three in China. Therefore, early diagnosis and comprehensive treatment are the key to the treatment of gastric cancer. Because of the concept of targeted therapy, it is helpful to study the expression patterns of gastric cancer-related genes in tissues and blood at the molecular level for the early diagnosis and prognosis of gastric cancer, so as to improve the therapeutic effect of gastric cancer. The abnormal expression of tumor-related genes in tissues and peripheral blood is involved in regulating the occurrence, development, invasion, proliferation, apoptosis and metastasis of tumors. Dynamic changes in different clinical stages, degrees of differentiation and prognosis provide a theoretical basis for early diagnosis of tumors. The purpose of this study is to investigate the relationship between the expression of microRNAs-126 and microRNAs-199a in gastric cancer tissues and serum and their clinicopathological features, and to analyze the diagnostic value of serum microRNAs-126 and microRNAs-199a, so as to provide a basis for the study of microRNAs as a biomarker in the diagnosis of gastric cancer, the diagnosis of the disease and the pathogenesis. Methods: 42 gastric cancer patients with definite preoperative pathological diagnosis admitted to the Second Affiliated Hospital of Nantong University from June 2016 to December 2016 were selected as the experimental group, and 60 healthy people of the same age in the physical examination center of the Affiliated Hospital of Nantong University were selected as the control group. The cancer tissues and distant cancer control tissues (more than 5 cm away from cancer tissues) were frozen to confirm gastric cancer within 30 minutes after operation. The tissues were frozen in liquid nitrogen for reserve. The expression of microRNA-199a in tissues and serum was detected by standard carcinoembryonic antigen (CEA) in peripheral blood of patients before operation and 1 week after operation. The reference value was 0-10 ng/L. Results: 1. In gastric cancer tissues, the relative expression level of microRNA-126 in cancer tissues was (7.17 (+ 2.62) (t = 7.276, P 0.05). There was a statistical difference between the two groups. The expression of microRNA-126 in cancer tissue was related to tumor size, clinical stage and degree of tissue differentiation; the relative expression level of microRNA-199a in cancer tissue was higher than that in distant cancer control group (2.12 + 1.11) (t = 3.908, P 0.05). The expression of microRNA-199a in cancer tissue was significantly different from that in clinical stage, depth of invasion and lymph node. Metastasis related. 2. In the serum of gastric cancer patients, the relative expression of microRNA-126 in preoperative serum (2.49 + 3.36) was lower than that in postoperative serum (7.83 + 2.61) (t = 6.316, P 0.05); the relative expression in postoperative serum was lower than that in healthy controls (9.60 + 4.01) (t = 4.338, P 0.05), and there was statistical difference between the two groups. The relative expression of Mi-199a in serum before operation was higher than that after operation (14.03 [6.02] (t = 6.778, P 0.05); the relative expression of Mi-199a in serum after operation was higher than that in healthy control group (5.81 [4.67] (t = 7.684, P 0.05), and there was statistical difference between the two groups. The area under the ROC curve was 0.823, and the area under the serum AUC was 0.776; the area under the ROC curve was 0.862 and the serum AUC was 0.918; the area under the ROC curve of CEA was 0.537.4. Pearson correlation analysis showed that the area under the ROC curve was 0.823 and 0.776 respectively. There was a positive correlation between the relative expression of microRNAs-126 in gastric cancer tissues and preoperative serum (r = 0.65, P 0.01). Conclusion: 1. The expression of microRNAs-126 in gastric cancer tissues and serum was down-regulated, and the expression of microRNAs-199a was up-regulated. 2. The expression of serum microRNAs-126 in gastric cancer patients was correlated with the occurrence and development of gastric cancer. The expression of serum microRNA-126 and microRNA-199a can be used as one of the markers to evaluate the severity of gastric cancer. 3. The expression of serum microRNA-126 and microRNA-199a has better diagnostic value for gastric cancer than serum CEA. There was a positive correlation between the expression of serum microRNA-126 and microRNA-199a, which might be useful biomarkers for the diagnosis of gastric cancer.
【學(xué)位授予單位】：揚(yáng)州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.2

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本文編號(hào)：2191609