首页|循环miR-17-5p/miR-362-5p组合作为肺鳞癌血液生物标志物的研究

循环miR-17-5p/miR-362-5p组合作为肺鳞癌血液生物标志物的研究

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目的 筛选原发性肺鳞癌(LUSC)患者血液中差异表达的可用作诊断生物标志物的微RNA(miRNA).方法 通过miRNA微阵列随机筛选6例LUSC患者和6例年龄匹配的健康对照者全血中差异表达的miRNA,然后通过实时聚合酶链式反应在35例LUSC患者和33例健康对照者中验证候选差异表达miRNA.结果 在LUSC患者中发现了6种差异表达的血清miRNAs(miR-17-5p、miR-205-5p、miR-362-5p、miR-21-5p、miR-210-3p、miR-222-3p).其中miR-17-5p、miR-362-5p、miR-21-5p可以良好地区分LUSC组和对照组,受试者操作特征(ROC)曲线下面积(AUC)均>0.8(P<0.001),显示出比其他3种miRNAs相对更高的AUC、敏感性和特异性.而且miR-17-5p、miR-362-5p可以良好地区分早期(TNMⅠ-Ⅱ期)LUSC患者和健康对照志愿者,AUC值均>0.8(P<0.001).TCGA数据库的数据显示,miR-17-5p或miR-362-5p的高表达预示着LUSC患者(n=332例)的总生存率较差(P<0.05).以是否发生LUSC为因变量,以miR-17-5p和 miR-362-5p的表达情况为自变量建立Logistic回归诊断模型(2-miRNA组合),2-miRNA组合模型的AUC是0.9570,灵敏度和特异性分别为92.65%和92.31%.生物信息学分析表明,这2种miRNAs可能参与多种癌症相关通路.结论 miR-17-5p和miR-362-5p可以高准确度区分LUSC患者和健康对照组,并有效地预测LUSC患者的不良生存率,考虑可以将2-miRNA组合作为LUSC诊断的候选生物标志物.
Study on circulating miR-17-5p/miR-362-5p as a blood biomarker for lung squamous cell carcinoma
Objective To screen differentially expressed microRNAs(miRNAs)in the blood of patients with lung squamous cell carcinoma(LUSC),which can be used as diagnostic biomarkers.Methods The differen-tially expressed mirnas in whole blood of 6 LUSC patients and 6 age-matched healthy controls were randomly selected by miRNA microarray,and then the candidate differentially expressed miRNAs were verified by real-time polymerase chain reaction in 35 LUSC patients and 33 healthy controls.Results Six differently ex-pressed miRNAs in serum samples(miR-17-5p,miR-205-5p,miR-362-5p,miR-21-5p,miR-210-3p,and miR-222-3p)were found in LUSC patients.Among them,miR-17-5p,miR-362-5p and miR-21-5p could well distinguish the LUSC group and the control group,and the area under the receiver operator characteristic curve(ROC AUC)were all>0.8(P<0.001),indicating relatively higher AUC,sensitivity and specificity than the other three miRNAs.Moreover,miR-17-5p and miR-362-5p could well distinguish the early stage(TNM stage Ⅰ-Ⅱ)LUSC patients from healthy control volunteers,with AUC values>0.8(P<0.001).Data from the TCGA database showed that high expression of miR-17-5p or miR-362-5p predicted poor overall survival in LUSC patients(n=332 cases)(log-rank P<0.05).Logistic regression analysis was performed with the occur-rence of LUSC as the dependent variable and the expression of miR-17-5p and miR-362-5p combination(2-miRNA panel)as the indepedent variable,to determine whether the 2-miRNA combination could improve the diagnostic value.The AUC of 2-miRNA panel was 0.9570,and the sensitivity and specificity were 92.65%and 92.31%,respectively.Bioinformatics analysis suggests that these two miRNAs may be involved in a variety of cancer-related pathways.Conclusion MiR-17-5p and miR-362-5p can accurately distinguish between LUSC patients and healthy control groups,and effectively predict the adverse survival rate of LUSC patients.It is considered that 2-miRNA panel can be used as candidate biomarkers for LUSC diagnosis,but further research is needed to demonstrate it.

lung squamous cell carcinomadiagnoseprognosismicroRNAblood biomarkercirculating microRNA

杨贵哲、王懿、刘合代、杨志勇

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上海健康医学院附属崇明医院 肿瘤科,上海 202150

肺鳞癌 诊断 预后 微RNA 血液生物标志物 循环微RNA

上海市科技创新行动计划资助项目

CKY2019-18

2024

兰州大学学报(医学版)
兰州大学

兰州大学学报(医学版)

CSTPCD
影响因子:0.641
ISSN:1000-2812
年,卷(期):2024.50(6)
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