miR-421和miR-196b-3p在胃癌癌前病变和早期胃癌诊断中的潜在价值  

Potential value of miR-421 and miR-196b-3p in diagnosis of gastric precancerous lesions and early gastric cancers

作　　者：王文怡[1] 余静恬 甘程 WANG Wenyi;YU Jingtian;GAN Cheng(Department of Clinical Laboratory,Affiliated Tianyou Hospital,Wuhan University of Science and Technology,Wuhan,Hubei 430000,China)

机构地区：[1]武汉科技大学附属天佑医院检验科,湖北武汉430000

出　　处：《检验医学与临床》2024年第6期726-732,共7页Laboratory Medicine and Clinic

基　　金：湖北省卫生健康委科研项目(WJ2019F164)。

摘　　要：目的研究血浆miR-421和miR-196b-3p作为诊断胃癌癌前病变和早期胃癌新型潜在生物标志物的临床意义。方法(1)发现集:于2018年12月1日至12月31日采集早期胃癌患者(早期胃癌组)、癌前病变患者(癌前病变组)和健康志愿者(NC组)的血浆标本各3例,用作miRNA微阵列分析。借用TCGA数据证实候选miRNA在癌症组织中的表达。(2)验证集:于2019年1月1日至2023年1月1日共采集90例胃癌患者(胃癌组)、89例癌前病变患者(癌前病变组)和45例健康志愿者(NC组)的血浆标本。通过定量实时聚合酶链反应测定候选miRNA水平。比较各组候选miRNA及常规肿瘤标志物[铁蛋白、甲胎蛋白(AFP)、癌胚抗原(CEA)、CA211、CA50、CA125、CA199、CA153、CA242、CA724]水平;通过受试者工作特征(ROC)曲线分析比较候选miRNA与常规肿瘤标志物的诊断价值。结果(1)发现集:通过miRNA微阵列筛选,与NC组相比,miR-421和miR-196b-3p水平在早期胃癌组和癌前病变组明显上调(P<0.05)。TCGA数据证实,与正常胃黏膜相比,miR-421在胃癌组织中呈高表达(P<0.001)。(2)验证集:与NC组相比,癌前病变组和胃癌组血浆miR-421、miR-196b-3p水平明显上调(P<0.05),且胃癌组血浆miR-421、miR-196b-3p水平高于癌前病变组(P<0.001)。ROC曲线分析结果显示,血浆miR-421对胃癌的诊断价值最高,曲线下面积(AUC)为0.931(95%CI:0.889~0.972),高于CEA、CA125、CA199、CA724、CA211、CA50诊断胃癌的AUC(P<0.05);miR-196b-3p诊断胃癌的AUC[0.804(95%CI:0.733~0.875)]也高于CEA、CA125、CA199和CA724诊断胃癌的AUC(P<0.05);miR-421和miR-196b-3p也可用于早期胃癌诊断,AUC分别为0.942(95%CI:0.886~0.997)和0.809(95%CI:0.708~0.910);血浆miR-421和miR-196b-3p诊断癌前病变的AUC分别为0.788(95%CI:0.714~0.863)和0.648(0.556~0.741),miR-421诊断癌前病变的AUC均高于miR-196b-3p、铁蛋白、CA50诊断癌前病变的AUC(P<0.05)。血浆miR-421和miR-196b-3p在胃癌Ⅰ期病例中的水平与Ⅱ、Ⅲ/Ⅳ期相Objective To study the clinical significance of plasma miR-421 and miR-196b-3p as novel potential biomarkers for the diagnosis of precancerous lesions and early gastric cancer.Methods(1) Discovery set:each 3 plasma samples were collected from the patients with early gastric cancer(early gastric cancer group),the patients with precancerous lesions(precancerous lesions group) and 3 healthy volunteers(NC group) for conducting the miRNA microarray analysis from December 1 to December 31,2018.The expression of candidate miRNA in cancer tissues was confirmed by using TCGA data.(2) Validation set:the plasma samples were collected from 90 patients with gastric cancer(gastric cancer group),89 patients with precancerous lesions(precancerous lesions group) and 45 healthy volunteers(NC group) from January 1,2019 to January 1,2023.The candidate miRNA content was detected by quantitative real-time polymerase chain reaction.The levels of candidate miRNAs and conventional tumor markers [ferritin,alpha fetoprotein(AFP),carcinoembryonic antigen(CEA),CA211,CA50,CA125,CA199,CA153,CA242,CA724] in each group were compared.The diagnostic value was analyzed and compared between the candidate miRNA and conventional tumor markers by the receiver operating characteristic(ROC) curve.Results(1) In the discovery set:the miRNA microarray screening showed that compared with the NC group,the levels of miR-421 and miR-196b-3p were significantly up-regulated in the early gastric cancer group and precancerous lesion group(P<0.05).The TCGA data confirmed that miR-421 in gastric cancer tissue was highly expressed compared to normal gastric mucosa(P<0.001).(2) In the validation set:compared with the NC group,the plasma miR-421 and miR-196b-3p levels in the precancerous and gastric cancer groups were significantly upregulated(P<0.05),moreover the plasma miR-421 and miR-196b-3p levels in the gastric cancer group were higher than those in the precancerous group(P<0.001).The ROC curve analysis showed that plasma miR-421 had the highest diagnostic value fo

关 键 词：早期诊断 癌前病变 miR-421 miR-196b-3p miRNA微阵列 胃癌 

分 类 号：R735.2[医药卫生—肿瘤] R446[医药卫生—临床医学]