【摘要】 目的 miR-182在不同类型的癌症中可起癌基因的作用被发现在胃癌组织中的表达增高且其高表达与病情进展及不良预后有关,然而目前关于血清miRNA-182的表达水平及其对胃癌的诊断效能的研究报道较少。文中探讨血清miRNA-182联合癌胚抗原(CEA)对胃癌的诊断效能及临床意义。方法选择2017年6月-2018年6月在贵州省人民医院消化内科经病理学检查证实且均未进行治疗的68例胃癌患者(胃癌组),行胃镜病理检查确诊的65例胃炎患者(胃炎组)以及健康体检人群65例(对照组)。采用原位杂交检测胃癌组织及癌旁组织中miRNA-182表达;采用实时荧光定量PCR法(qRT-PCR)检测血清miRNA-182的相对表达量及临床常规检测CEA,并分析miRNA-182的表达水平与患者临床病理特征的关系;采用ROC曲线分析miRNA-182、CEA及两者联合对胃癌的诊断效能。结果胃癌患者组织中miRNA-182阳性表达率(76.47%)显著高于癌旁组织(22.06%),且Ⅲ期+Ⅳ期胃癌组织中miRNA-182阳性表达率(95.24%)显著高于Ⅰ+Ⅱ期胃癌组织中miRNA-182阳性表达率(46.15%),差异均有统计学意义(P<0.05);胃癌患者血清中miRNA-182相对表达量(5.17±0.60)、CEA表达为15.39(10.25～18.37)ng/mL分别高于胃炎患者(4.29±0.63)和2.98(2.41～4.67)ng/mL以及对照组(4.26±0.59)、2.92(2.55～4.63)ng/mL;Ⅰ+Ⅱ期胃癌患者血清miRNA-182相对表达量(4.84±0.57)及CEA的表达水平10.12(4.55～15.48)ng/mL均低于Ⅲ期患者(5.40±0.49)、16.82(15.15～20.63)ng/mL和Ⅳ期患者(5.34±0.60)、17.36(14.66～19.09)ng/mL,差异有统计学意义(P<0.05)。单因素分析结果发现,miRNA-182高表达与肿瘤TNM分期、分化程度、转移有关(P<0.05)。ROC曲线分析结果显示,miRNA-182诊断胃癌的ROC曲线下面积为0.850(95%CI 0.786～0.914),其相应的灵敏性和特异度分别为73.5%和84.6%;CEA诊断胃癌的ROC曲线下面积为0.947(95%CI 0.913～0.980),其相应的灵敏性和特异度分别为83.8%和73.4%;两指标联合诊断胃癌的ROC曲线下面积为0.967(95%CI 0.943～0.991),其相应的灵敏性和特异度分别为94.1%和86.2%,且两指标联合诊断胃癌的准确性为90.2%,均优于单个指标(78.9%、79.7%)。结论血清miRNA-182联合CEA检测可提高胃癌诊断的灵敏性和准确性,对胃癌早期发现及治疗具有一定的临床价值。更多还原

【Abstract】 Objective miRNA-182 can play a role of oncogene in different types of cancer. It has been found that the expression of miRNA-182 is increased in gastric cancer tissues, and its high expression is related to the disease progression and poor prognosis. However, there are few reports on the expression level of serum miRNA-182 and its diagnostic efficacy for gastric cancer. Therefore, this study was to explore the diagnostic efficacy and clinical significance of serum miRNA-182 combined with carcinoembryonic antigen(CEA) in gastric cancer. Methods From June 2017 to June 2018, 68 patients with gastric cancer who were confirmed by pathological examination before treatment, 65 patients with gastritis who were confirmed by gastroscopy, and 65 healthy people were selected in the Department of Gastroenterology at the Hospital of Guizhou Province. In situ hybridization was used to detect the expression of miRNA-182 in gastric cancer tissues and adjacent tissues. Real-time fluorescence quantitative PCR(qRT-PCR) was used to detect the relative expression of serum miRNA-182 and clinical routine CEA. The relation between the expression level of miRNA-182 and the clinicopathological characteristics of patients was analyzed. Receiver operating characteristic(ROC) curve was used to analyze the diagnostic efficacy of miRNA-182, CEA and their combination in gastric cancer. Results In the gastric cancer group, the positive expression rate of miRNA-182 in gastric cancer tissues(76.47%) was significantly higher than that in adjacent tissues(22.06%)(P<0.05), and the positive expression rate of miRNA-182 in stage III+IV gastric cancer tissues(95.24%) was significantly higher than that in stage I+II gastric cancer tissues(46.15%)(P<0.05). The relative expression of miRNA-182(5.17±0.60) and CEA [15.39(10.25-18.37) ng/mL] in serum of patients with gastric cancer were higher than those of patients with gastritis(4.29±0.63), [2.98(2.41-4.67) ng/mL] and control group(4.26±0.59), [2.92(2.55-4.63) ng/mL]. With the increase of TNM stages of gastric cancer, the relative expression of miRNA-182 and CEA levels in different stages were significantly different(P<0.05). The relative expression of miRNA-182(4.84±0.57) and CEA [10.12(4.55-15.48) ng/ml] in patients with stage I+II gastric cancer were significantly lower than those with stage III(5.40±0.49), [16.82(15.15-20.63) ng/mL], and stage IV(5.34±0.60) and [17.36(14.66-19.09) ng/mL](P< 0.05). Univariate analysis showed that the overexpression of miRNA-182 was associated with TNM stage, differentiation and metastasis(P<0.05). ROC curve analysis showed that the area under ROC curve of miRNA-182 was 0.850(95% CI 0.786-0.914), and the corresponding sensitivity and specificity were 73.5% and 84.6% respectively, while the area under ROC curve of CEA was 0.947(95% CI 0.913-0.980), and its sensitivity and specificity were 83.8% and 73.4% respectively. The area under ROC curve of the combined diagnosis was 0.967(95% CI 0.943-0.991), and the sensitivity and specificity were 94.1% and 86.2%, and the accuracy of the combined diagnosis was 90.2%, which was better than that of the single diagnosis(78.9%, 79.7%). Conclusion The detection of serum miRNA-182 combined with CEA can improve the sensitivity and accuracy of gastric cancer diagnosis, and has a certain clinical value for early detection and treatment of gastric cancer.更多还原