血清外周miRNAs差异表达在脊柱结核中的临床意义

doi:10.3969/j.issn.1006-6233.2023.12.05

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摘要 目的: 探讨血清外周微小RNA(miRNAs)差异表达在脊柱结核中的临床意义。方法: 自2020年5月至2023年5月,纳入本院脊柱骨科收治的50例脊柱结核患者(实验组)和30例健康体检者(对照组)为研究对象。使用miRCURYTM LNA阵列(v.18.0)在10例实验组患者和10例对照组健康人群中筛选miRNAs表达谱。通过RT-qPCR在研究队列中验证了10个选择的miRNAs的表达水平。选择hsa-miR-4708-3p、hsa-miR-5100、hsa-miR-493-3p用于构建基于miRNAs的脊柱结核诊断模型(STB模型)。受试者操作特征(ROC)曲线分析STB模型对脊柱结核的诊断价值。结果: 与健康人群相比,在脊柱结核患者血清中发现288种miRNAs差异表达(123种上调,165种下调)(倍数变化>2,P<0.05)。RT-qPCR分析证实,与对照组相比,实验组血清样本中hsa-miR-4708-3p、hsa-miR-5100水平显著上调(P<0.05),hsa-miR-493-3p水平显著下调(P<0.05)。基于hsa-miR-4708-3p、hsa-miR-5100、hsa-miR-493-3p的表达水平作为变量,建立的多元Logistic回归模型如下:0.582+1.055×(hsa-miR-4708-3p)+0.811×(hsa-miR-5100)-0.970×(hsa-miR-493-3p)。与对照组相比,实验组STB模型评分显著升高(0.32±0.04vs0.65±0.08,t=6.09,P<0.001)。当临界值设置为0.46时,STB模型鉴别脊柱结核的ROC曲线下面积(AUC)为0.911,灵敏度为88.9%,特异度为77.0%。CRP和红细胞沉降率异常的脊柱结核患者的STB模型评分显著高于CRP和红细胞沉降率正常的脊柱结核患者(P<0.05)。STB模型评分与CRP、红细胞沉降率呈显著正相关(r=0.633、0.499,均P<0.001)。结论: hsa-miR-4708-3p、hsa-miR-5100和hsa-miR-493-3p在脊柱结核患者外周血中有稳定的差异表达,包含这三种miRNAs的诊断模型具有较好的脊柱结核诊断性能。

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	付海平
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关键词 ：脊柱结核, 外周血, 微小RNA, 诊断模型, 差异表达

Abstract：Objective: To explore the clinical significance of differential expression of serum peripheral micrornas(miRNAs)in spinal tuberculosis. Methods: From May 2020 to May 2023, 50 patients with spinal tuberculosis (experimental group) and 30 healthy people (control group) admitted to the Department of Spinal Orthopaedics of our hospital were taken as the research objects. MiRCURYTM LNA array (v.18.0) was used to screen the expression profile of miRNAs in 10 experimental patients and 10 healthy controls. The expression levels of 10 selected miRNAs were verified by RT-qCPR in the research cohort. Hsa-miR-4708-3p, hsa-miR-5100 and hsa-miR-493-3p were selected to construct the spinal tuberculosis diagnosis model (STB model) based on miRNAs. Diagnostic value of STB model in spinal tuberculosis by analyzing receiver operating characteristic (ROC) curve. Results: Compared with healthy people, 288 kinds of miRNAs were found in the serum of patients with spinal tuberculosis(123 kinds were up-regulated and 165 kinds were down-regulated) (multiple change>2, P<0.05). RT-qPCR analysis confirmed that compared with the control group, the levels of hsa-miR-4708-3p and hsa-miR-5100 in serum samples of the experimental group increased significantly(P<0.05), and the level of hsa-miR-493-3p decreased significantly(P<0.05). Based on the expression levels of hsa-miR-4708-3p, hsa-miR-5100 and hsa-miR-493-3p as variables, a multivariate logistic regression model was established as follows: 0.582+1.055×(hsa-miR-4708-3p)+0.811× (hsa-miR-5100)-0.970×(hsa-miR-493-3p). Compared with the control group, the STB model score in the experimental group was significantly higher (0.32±0.04 vs 0.65±0.08, t=6.09, P<0.001). When the critical value was set to 0.46, the area under ROC curve (AUC) of STB model in identifying spinal tuberculosis was 0.911, with sensitivity of 88.9% and specificity of 77.0%. The STB model scores of patients with spinal tuberculosis with abnormal CRP and erythrocyte sedimentation rate were significantly higher than those with normal CRP and erythrocyte sedimentation rate (P<0.05). The score of STB model was positively correlated with CRP and erythrocyte sedimentation rate (r=0.633, 0.499, all P<0.001). Conclusion: Hsa-miR-4708-3p, hsa-miR-5100 and hsa-miR-493-3p have stable differential expressions in peripheral blood of patients with spinal tuberculosis, and the diagnostic model containing these three miRNAs has good diagnostic performance for spinal tuberculosis.

Key words： Spinal tuberculosis Peripheral blood MicroRNA Diagnostic model Difference show

基金资助:2021年度内蒙古自治区卫生健康科技计划项目,(编号:202101013)

引用本文:

付海平, 王飞, 郇颜强, 阿拉木苏. 血清外周miRNAs差异表达在脊柱结核中的临床意义[J]. 河北医学, 2023, 29(12): 1957-1962.
FU Haiping, WANG Fei, HAO Yanqiang, et al. Clinical Significance of Differential Expression of Serum Peripheral miRNAs in Spinal Tuberculosis. HeBei Med, 2023, 29(12): 1957-1962.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.12.05 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I12/1957

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