血浆miRNA在肺癌早期筛查中作用的病例对照研究

A case-control study on the role of plasma miRNA in early screening of lung cancer

目的:探讨miR-122-5p等miRNA在早期肺癌患者血浆中的表达水平及其与肺癌发病风险的关联性。方法:运用高通量测序技术筛选在早期肺癌患者和对照者血浆中差异表达的miRNA,通过实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测miRNA的表达。采用性别、年龄±5岁进行1∶2匹配的病例对照研究,使用条件Logistic回归分析miRNA与肺癌发病风险的关联。结果:早期肺癌组血浆miR-122-5p、miR-199a-5p、miR-221-3p、miR-27b-3p和miR-99a-5p的表达水平均显著高于对照组(P<0.01);用于检测早期肺癌时,miR-199a-5p的灵敏度可达95.8%,miR-99a-5p的特异度可达81.2%;血浆miR-122-5p、miR-199a-5p、miR-221-3p、miR-27b-3p和miR-99a-5p的表达与肺癌发病风险升高存在显著关联,第四分位数组的肺癌发病风险较高,分别是第一分位数组的9.613倍(95%CI:1.488~62.118,P_(trend)=0.011)、23.863倍(95%CI:2.208~257.938,P_(trend)=0.007)、27.416倍(95%CI:2.575~291.919,P_(trend)=0.003)、23.626倍(95%CI:2.044~273.070,P_(trend)=0.005)和72.504倍(95%CI:3.519~1493.742,P_(trend)=0.004)。结论:miR-122-5p、miR-199a-5p、miR-221-3p、miR-27b-3p和miR-99a-5p是肺癌发病的危险因素。

Objective:To investigate the expression levels of miR-122-5p and other miRNA in the plasma of patients with early lung cancer and their correlation with the risk of lung cancer.Methods:High-throughput sequencing technology was used to screen the differentially expressed miRNA in the plasma of patients with early lung cancer and controls,and the expression of miRNA was detected by quantitative real-time PCR(qRT-PCR).A 1∶2 matched case-control study was conducted using gender and age±5 years old,and conditional Logistic regression was used to analyze the association between miRNA and the risk of lung cancer.Results:The expression levels of plasma miR-122-5p,miR-199a-5p,miR-221-3p,miR-27b-3p and miR-99a-5p in the early lung cancer group were significantly higher than those in the control group(P<0.01).When detecting early lung cancer,the sensitivity of miR-199a-5p can reach 95.8%,and the specificity of miR-99a-5p can reach 81.2%.The expression levels of plasma miR-122-5p,miR-199a-5p,miR-221-3p,miR-27b-3p and miR-99a-5p were significantly associated with the increased risk of lung cancer.The risk of lung cancer in the fourth quantile group was higher than that in the first quantile group,reaching 9.613 times(95%CI:1.488~62.118,P_(trend)=0.011),23.863 times(95%CI:2.208~257.938,P_(trend)=0.007),27.416 times(95%CI:2.575~291.919,P_(trend)=0.003),23.626 times(95%CI:2.044~273.070,P_(trend)=0.005)and 72.504 times(95%CI:3.519~1493.742,P_(trend)=0.004),respectively.Conclusion:miR-122-5p,miR-199a-5p,miR-221-3p,miR-27b-3p and miR-99a-5p are risk factors for the onset of lung cancer.