胃癌组织及血清miR-126、miR-199a表达的临床价值研究

发布时间：2018-08-19 12:08

【摘要】：背景和目的:胃癌是常见的恶性肿瘤之一,它的早期诊断率低、治疗效果不理想,尽管其发病率在世界范围内有所下降,但在我国胃癌的发病率和死亡率仍居恶性肿瘤的前三位,因此尽早诊断,综合治疗是治疗胃癌的关键。近年来,随着基因靶向治疗理念的出现,在分子水平上探讨胃癌相关基因在组织和血液中的表达模式,将有助于胃癌的早期诊断,评估预后,从而改善胃癌的治疗效果。miRNA是一种广泛存在于生物体内的非编码单链小分子RNA,研究证实,miRNAs在肿瘤的组织和外周血中存在异常表达,参与调控肿瘤相关基因,影响肿瘤的发生、发展、侵袭、增殖、凋亡和转移,在不同的临床分期、不同分化程度和预后方面存在动态变化,为肿瘤的早期诊断提供了理论基础。然而miR-126、miR-199a在胃癌的发生、发展过程中表达的机制尚不十分清楚。本文旨在探讨miR-126、miR-199a在胃癌组织与血清中的表达与临床病理特征之间的关系,分析血清miR-126、miR-199a的诊断价值,为miRNAs作为诊断胃癌的生物学标志物、判断病情以及发病机制的研究提供依据。方法:收集南通大学附属第二医院于2016年06月至2016年12月住院期间胃肠外科收治的术前病理诊断明确的胃癌患者42例作为实验组。收集南通大学附属医院体检中心体检的年龄相仿的60例健康人群作为对照组。标本系胃癌根治术后新鲜标本,于手术后30 min内取其癌组织及远癌对照组织(距离癌组织5 cm以上)作快速冰冻以证实为胃癌,取下的组织放液氮中冻存备用。采集患者术前、术后1周的外周血各5 mL,采集健康对照组人群的外周血5 mL,采用实时定量PCR的方法检测miR-126、miR-199a在组织和血清中的表达情况。于术前和术后1周左右分别采集患者外周血5 mL送检验科作标准化癌胚抗原(CEA)检测,参考值为0～10ng/L。结果:1、在胃癌组织中,miR-126在癌组织中的相对表达水平(7.17±2.62)(t=7.276,P0.05),两组存在统计学差异;miR-126在癌组织中的表达与肿瘤大小、临床分期、组织分化程度有关;miR-199a在癌组织中的相对表达水平(12.04±2.27)高于远癌对照者(2.12±1.11)(t=3.908,P0.05),两组存在统计学差异;miR-199a在癌组织中的表达与肿瘤临床分期、浸润深度、淋巴结转移有关。2、在胃癌患者血清中,miR-126在术前血清的相对表达水平(2.49±3.36)低于术后(7.83±2.61)(t=6.316,P0.05);在术后血清中的相对表达水平低于健康对照者(9.60±4.01)(t=4.338,P0.05),两组存在统计学差异;miR-126在血清中的表达与肿瘤临床分期、组织分化程度有关;miR-199a在术前血清中的相对表达水平(30.04±5.04)高于术后(14.03±6.02)(t=6.778,P0.05);在术后血清中的相对表达水平高于健康对照者(5.81±4.67)(t=7.684,P0.05),两组存在统计学差异;miR-199a在血清中的表达与肿瘤临床分期、浸润深度有关。3、胃癌组织miR-126的诊断效率ROC曲线下面积AUC为0.823,血清AUC为0.776;胃癌组织miR-199a的诊断效率ROC曲线下面积AUC为0.862,血清AUC为0.918;CEA的诊断效率ROC曲线下面积AUC为0.537。4、Pearson相关分析显示,胃癌患者癌组织与术前血清中miR-126的相对表达水平呈正相关(r=0.484,P0.01);癌组织与术前血清中miR-199a的表达水平呈正相关(r=0.65,P0.01)。结论:1、胃癌组织和血清miR-126表达下调、miR-199a表达上调,两者均与胃癌的发生发展相关。2、胃癌患者血清miR-126的表达水平与临床分期和组织分化程度有关,miR-199a的表达水平与肿瘤浸润深度和临床分期有关。血清miR-126、miR-199a的表达,可以作为评估胃癌患者病情严重程度的标志之一。3、血清miR-126、miR-199a的表达对胃癌具有较好的诊断价值,两者均优于血清CEA;组织和血清miR-126、miR-199a的表达水平呈正相关,有望成为有价值的诊断胃癌的生物学标志物。
[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.
【学位授予单位】：扬州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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