miR-16联合Cripto-1、ANXA7诊断胃癌及其淋巴结转移的临床价值研究

The clinical value of miR-16 combined with Cripto-1 and ANXA7 in the diagnosis of gastric cancer and its lymph node metastasis

目的探讨microRNA-16(miR-16)联合畸胎瘤衍生生长因子(Cripto-1)、膜联蛋白A7(ANXA7)诊断胃癌及其淋巴结转移的临床价值。方法选取2017年6月至2019年9月南京大学医学院附属鼓楼医院内科治疗的胃部疾病患者546例,根据胃癌诊断标准分为胃癌组(121例)和非胃癌组(425例)。所有胃癌患者根据胃癌进展分为早期胃癌组(44例)、进展期胃癌组(77例),根据淋巴结是否转移分为淋巴结转移组(71例)、无淋巴结转移组(50例)。选择同期该院健康体检者50例作为对照组。采用实时荧光定量PCR检测血清miR-16水平;采用酶联免疫吸附测定检测ANXA7和Cripto-1水平;采用Pearson相关分析胃癌患者血清miR-16水平与ANXA7、Cripto-1水平的相关性。采用受试者工作特征曲线(ROC曲线)分析miR-16、ANXA7、Cripto-1诊断胃癌及其淋巴结转移的价值。结果胃癌组血清miR-16、ANXA7、Cripto-1水平均高于非胃癌组和对照组(P<0.05);进展期胃癌组血清miR-16、ANXA7、Cripto-1水平均高于早期胃癌组(P<0.05);淋巴结转移组血清miR-16、ANXA7、Cripto-1水平均高于无淋巴结转移组(P<0.05);miR-16、ANXA7、Cripto-1诊断胃癌的最佳临界值分别为11.81、71.51μg/L、2.26μg/L,3项指标联合诊断胃癌的ROC曲线下面积(AUC)为0.996,其灵敏度(95.04%)和特异度(97.26%)较高;miR-16、ANXA7、Cripto-1诊断胃癌淋巴结转移的最佳临界值分别为18.95、78.93μg/L、3.73μg/L,3项指标联合诊断胃癌淋巴结转移的AUC为0.996,其灵敏度(97.18%)和特异度(96.00%)较高;胃癌患者血清miR-16水平与ANXA7、Cripto-1水平均呈正相关(r=0.465、0.519,P<0.05)。结论血清miR-16、ANXA7、Cripto-1水平在胃癌患者中明显升高,且与胃癌发生发展相关,3项指标联合检测在诊断胃癌及其淋巴结转移中有一定价值。

Objective To investigate the clinical value of microRNA-16(miR-16)combined with teratoma-derived growth factor(Cripto-1)and Annexin A7(ANXA7)in the diagnosis of gastric cancer and its lymph node metastasis.Methods A total of 546 patients with gastric diseases treated by the Drum Tower Hospital Affiliated Nanjing University Medical School from June 2017 to September 2019 were divided into gastric cancer group(121 cases)and non-gastric cancer group(425 cases)according to the diagnostic criteria for gastric cancer.All gastric cancer patients were divided into early gastric cancer group(44 cases)and advanced gastric cancer group(77 cases)according to the progress of gastric cancer;according to whether the lymph node metastasis or not,there were divided into lymph node metastasis group(71 cases)and non-lymph node metastasis group(50 cases).Selected 50 cases of healthy physical examination in this hospital during the same period as the control group.Real-time fluorescence quantitative was used to detect the level of miR-16;enzyme-linked immunosorbent assay was used to detect the levels of ANXA7 and Cripto-1;Pearson correlation analysis was used to analyze the correlation between serum miR-16,ANXA7 and Cripto-1 levels in patients with gastric cancer.The receiver operating characteristic curve(ROC curve)was used to analyze the value of miR-16,ANXA7,and Cripto-1 in the diagnosis of gastric cancer and its lymph node metastasis.Results The levels of serum miR-16,ANXA7 and Cripto-1 in the gastric cancer group were higher than those in the non-gastric cancer group and the control group(P<0.05).The levels of serum miR-16,ANXA7 and Cripto-1 in the advanced gastric cancer group were higher than those in the early gastric cancer group(P<0.05).The levels of serum miR-16,ANXA7 and Cripto-1 in the lymph node metastasis group were higher than those in the non-lymph node metastasis group(P<0.05).The optimal cut-off values of miR-16,ANXA7,and Cripto-1 for the diagnosis of gastric cancer were 11.81,71.51μg/L,and 2.26μg/L,respectively.The area under the curve(AUC)for the combined diagnosis of gastric cancer by the three indicators was 0.996,and its sensitivity(95.04%)and specificity(97.26%)were higher.The optimal cut-off values of miR-16,ANXA7,and Cripto-1 for diagnosing gastric cancer lymph node metastasis were 18.95,78.93μg/L,and 3.73μg/L,respectively.The AUC of the three indicators combined to diagnose gastric cancer lymph node metastasis was 0.996,and its sensitivity(97.18%)and specificity(96.00%)were higher.Serum miR-16 level in patients with gastric cancer was positively correlated with ANXA7 and Cripto-1 levels(r=0.465,0.519,P<0.05).Conclusion The levels of serum miR-16,ANXA7 and Cripto-1 are significantly increased in patients with gastric cancer and are related to the occurrence and development of gastric cancer.The combined detection of the three indicators has certain value in the diagnosis of gastric cancer and its lymph node metastasis.