【摘要】 目的 探索微小RNA let-7b-5p用于早期诊断非小细胞肺癌（non-small-cell lung cancer,NSCLC）患者的可行性。方法 从Gene Expression Omnibus(GEO)数据库获取GSE152702、GSE171517、GSE27486以及GSE40738原始数据集，共包含145例NSCLC患者（NSCLC组）和83位健康人（对照组）的血液样本数据。NSCLC组数据涵盖肺腺癌（lung adenocarcinoma,LUAD）和肺鳞癌（lung squamous cell carcinoma,LUSC）。采用Wilcoxon秩和检验和标准化均数差（standardized mean difference,SMD）比较NSCLC组和对照组的let-7b-5p表达水平。通过受试者工作特征（receiver operating characteristic,ROC）曲线的曲线下面积（area under the curve,AUC）以及诊断性meta分析的敏感度和特异度评估let-7b-5p诊断NSCLC(LUAD和LUSC)的效能。结果 GSE152702、GSE27486以及GSE40738数据集显示，let-7b-5p在LUAD患者的血液中低表达（均P<0.05）,GSE152702数据集还显示LUSC患者的血液中let-7b-5p表达低于对照组（P<0.05）。综合LUAD和LUSC组的SMD结果进一步明确NSCLC组血液中let-7b-5p表达较对照组下调（SMD=-0.50,95%CI:-0.75～-0.26）。ROC曲线和诊断性meta分析显示，血液中let-7b-5p的表达水平可区分NSCLC样本和正常样本（AUC=0.79，敏感度=0.71，特异度=0.76）。ROC曲线分析显示，let-7b-5p在NSCLC中的10个潜在靶基因[碱性亮氨酸拉链和W2结构域2(basic leucine zipper and W2 domains2,BZW2)、细胞分裂周期蛋白25A(cell division cycle 25A,CDC25A)、细胞分裂周期相关基因8(cell division cycle associated8, CDCA8)、Ⅲ型胶原α-1链（collagen typeⅢalpha 1 chain,COL3A1）、外纺锤体极样蛋白1(extra spindle pole bodies like 1,ESPL1)、高迁移率族AT-hook蛋白1(high mobility group AT-hook 1,HMGA1)、胰岛素样生长因子2结合蛋白3(insulin like growth factor 2 mRNA binding protein 3,IGF2BP3)、NME/NM23核苷二磷酸激酶4(NME/NM23 nucleoside diphosphate kinase 4,NME4)、葡萄糖磷酸变位酶2样蛋白1(phosphoglucomutase 2 like 1,PGM2L1)以及核糖核苷酸还原酶调节亚基M2(ribonucleotide reductase regulatory subunit M2,RRM2)]可区分LUAD与正常肺样本（AUC=0.765～0.980）以及区分LUSC与正常肺样本（AUC=0.749～0.997）。结论 检测血液中的let-7b-5p表达水平可能可作为诊断NSCLC（包括LUAD和LUSC）患者的有效手段。更多还原

【Abstract】 Objective To explore the practicality of utilizing microRNA let-7b-5p to facilitate the early diagnosis of patients with nonsmall-cell lung cancer(NSCLC). Methods Raw datasets GSE152702, GSE171517, GSE27486, and GSE40738 were collected from the Gene Expression Omnibus(GEO) database. These datasets collectively comprise blood sample data from 145 NSCLC patients(NSCLC group) and 83 healthy individuals(control group). The NSCLC group data encompass both lung adenocarcinoma(LUAD) and lung squamous cell carcinoma(LUSC). The differences in the expression levels of let-7b-5p between the NSCLC and control groups were analyzed using the Wilcoxon rank-sum test and the standardized mean difference(SMD). The diagnostic performance of let-7b-5p in diagnosing NSCLC and distinguishing between LUAD and LUSC was evaluated through the area under the curve(AUC) of receiver operating characteristic(ROC)curves and the sensitivity and specificity of diagnostic meta-analysis. Results The datasets GSE152702, GSE27486, and GSE40738demonstrated that the expression of let-7b-5p was down-regulated in the blood of patients with LUAD(all P<0.05). Additionally, the GSE152702 dataset showed that the expression of let-7b-5p in the blood of LUSC patients was lower than that in the control group(P<0.05).Combining the SMD results from LUAD and LUSC groups further confirmed the down-regulation of let-7b-5p expression in the blood of patients with NSCLC compared to that of the control group(SMD=-0.50, 95% CI:-0.75--0.26). ROC curves and diagnostic meta-analysis revealed that the expression level of let-7b-5p in the blood could distinguish between NSCLC samples and normal samples(AUC=0.79,sensitivity=0.71, specificity=0.76). ROC curves further showed that 10 potential target genes of let-7b-5p in NSCLC could differentiate not only between LUAD and normal lung samples(AUC: 0.765-0.980) but also between LUSC and normal lung samples(AUC: 0.749-0.997).These genes included basic leucine zipper and W2 domains 2(BZW2), cell division cycle 25A(CDC25A), cell division cycle associated 8(CDCA8), collagen type Ⅲ alpha 1 chain(COL3A1), extra spindle pole bodies like 1(ESPL1), high mobility group AT-hook 1(HMGA1),insulin like growth factor 2 mRNA binding protein 3(IGF2BP3), NME/NM23 nucleoside diphosphate kinase 4(NME4), phosphoglucomutase 2 like 1(PGM2L1) and ribonucleotide reductase regulatory subunit M2(RRM2). Conclusions The detection of let-7b-5p expression levels in the blood could potentially serve as an effective means for the diagnosis of patients with NSCLC including LUAD and LUSC.更多还原