[1]冷 洁a,焦旭峰b,胡咏汶c,等.结核性脑膜炎患者脑脊液中miR-200a，miR-4652-3p 水平表达对疾病严重程度和预后预测价值研究[J].现代检验医学杂志,2024,39(03):78-83+97.[doi:10.3969/j.issn.1671-7414.2024.03.013]
　LENG Jiea,JIAO Xufengb,HU Yongwenc,et al.Study on the Predictive Value of miR-200a and miR-4652-3p Levels in Cerebrospinal Fluid of Patients with Tuberculous Meningitis for Disease Severity and Prognosis[J].Journal of Modern Laboratory Medicine,2024,39(03):78-83+97.[doi:10.3969/j.issn.1671-7414.2024.03.013]
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结核性脑膜炎患者脑脊液中miR-200a，miR-4652-3p 水平表达对疾病严重程度和预后预测价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年03期
页码:
78-83+97
栏目:
论著
出版日期:
2024-05-15

文章信息/Info

Title:
Study on the Predictive Value of miR-200a and miR-4652-3p Levels in Cerebrospinal Fluid of Patients with Tuberculous Meningitis for Disease Severity and Prognosis
文章编号:
1671-7414（2024）03-078-07
作者:
冷 洁a; 焦旭峰b; 胡咏汶c; 柳 霞d
（青岛市中心医院北部院区/ 青岛市胸科医院 a. 疾控科；b. 医教科；c. 胸二科；d. 胸一科，山东青岛 266043）
Author(s):
LENG Jiea;  JIAO Xufengb;  HU Yongwenc;  LIU Xiad
（a. Disease Control Department; b. Medical Education Department; c. Thoracic Second Department; d. Thoracic First Department,North Campus of Qingdao Central Hospital/ Qingdao Chest Hospital, Shandong Qingdao 266043, China）
关键词:
结核性脑膜炎; miR-200a; miR-4652-3p
分类号:
R529.3；R446.14
DOI:
10.3969/j.issn.1671-7414.2024.03.013
文献标志码:
A
摘要:
目的 分析结核性脑膜炎（tuberculous meningItis, TBM）患者脑脊液miR-200a 和miR-4652-3p 表达及其对疾病严重程度和预后的预测价值。方法 选择2018 年1 月~2022 年12 月于青岛市胸科医院就诊的187 例结核性脑膜炎患者，按照病情程度分为Ⅰ期（n=62）、Ⅱ期（n=76）和Ⅲ期（n=49），根据预后情况分为预后良好组（n=131）和预后不良组（n=56）。qRT-PCR 法检测脑脊液miR-200a 和miR-4652-3 水平表达。Spearman 法分析miR-200a 和miR-4652-3p 与临床资料间相关性；ROC 曲线分析脑脊液miR-200a 和miR-4652-3p 水平对结核性脑膜炎患者疾病严重程度及预后的预测价值。多因素Logistic 回归分析预后不良影响因素。结果 Ⅰ期、Ⅱ期、Ⅲ期结核性脑膜炎患者脑脊液miR-200a（1.05±0.14，0.91±0.14，0.76±0.13） 和miR-4652-3p（0.92±0.11，0.78±0.11，0.65±0.10）表达水平依次降低，差异具有统计学意义（F=61.079，87.203，均P ＜ 0.001）。预后良好组患者脑脊液miR-200a（0.95±0.14）和miR-4652-3p（0.82±0.11）表达水平显著高于预后不良组患者（0.84±0.13，0.73±0.10），差异具有统计学意义（t=5.025，5.262，均P ＜ 0.05）；预后良好患者脑脊液腺苷脱氨酶和TNF-α，IL-23，LTB4，CRP，mRS 评分显著低于预后不良患者， 差异具有统计学意义（t=5.649，7.721，11.150，9.455，11.314，14.407， 均P＜ 0.05）。结核性脑膜炎患者脑脊液miR-200a 和miR-4652-3p 水平呈正相关（r=0.405，P ＜ 0.001）；miR-200a，miR-4652-3p 与LTB4，TNF-α，CRP，mRS 评分，IL-23，腺苷脱氨酶呈负相关（r=-0.472，-0.466，-0.461，-0.435，-0.422，-0.419；-0.459，-0.531，-0.471，-0.417，-0.513，-0.408，均P ＜ 0.05）。miR-200a，miR-4652-3p 预测患者疾病严重程度的AUC（95%CI）分别为0.881（0.825~0.923）和0.878（0.822~0.921），二者联合预测的AUC（95%CI）为0.945（0.902~0.973），高于单项检测，差异具有统计学意义（Z=3.008，2.960，all P=0.003）。脑脊液miR-200a 和miR-4652-3p 水平评估患者预后不良的AUC（95%CI）为0.749（0.681~0.809）和0.756（0.688~0.816），二者联合评估患者预后不良的AUC（95%CI））为0.839（0.778~0.889），高于二者单独检测，差异有统计学意义（Z=2.994，2.697，P=0.003，0.007）。腺苷脱氨酶[OR（95%CI）：1.106（1.033~1.185）]、miR-200a[OR（95%CI）：0.529（0.369~0.744）]、miR-4652-3p[OR（95%CI）：0.471（0.310~0.715）]、CRP[OR（95%CI）：4.423（1.459~13.412）]、TNF-α[OR（95%CI）：1.196（1.061~1.348）]、IL-23[OR（95%CI）：4.809（1.086~3.013）] 和LTB4[OR（95%CI）：1.327（1.064~1.655）] 为结核性脑膜炎患者预后不良的影响因素（均P ＜ 0.05）。结论 结核性脑膜炎患者脑脊液miR-200a 和miR-4652-3p 表达下调，与疾病严重程度及预后密切相关，二者联合能较好地预测结核性脑膜炎严重程度及预后，具有一定临床价值。
Abstract:
Objective To analyze the expression of microRNA (miR) -200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis(TBM) and their predictive value for disease severity and prognosis. Methods A total of 187 patients with tuberculous meningitis who visited Qingdao Chest Hospital from January 2018 to December 2022 were regarded and separated into stage I (n=62), stage II (n=76) and stage III (n=49) according to the severity of the condition. There were 131 cases in the good prognosis group and 56 cases in the poor prognosis group according to the prognosis. The qRT-PCR method was applied to detect the expression levels of miR-200a and miR-4652-3p in cerebrospinal fluid. Spearman method was used to analyze correlation among miR-200a, miR-4652-3p and clinical data. ROC curve was applied to analyze the predictive value of cerebrospinal fluid miR-200a and miR-4652-3p levels in evaluating the severity and prognosis of tuberculosis meningitis patients. Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in patients. Results The expression levels of miR-200a (1.05±0.14, 0.91±0.14, 0.76±0.13) and miR-4652-3p (0.92±0.11, 0.78±0.11, 0.65±0.10) in the cerebrospinal fluid of patients with stage I, II, and III tuberculous meningitis were decreased sequentially, and the differences were significant (F=61.079, 87.203, all P<0.05). The expression levels of miR-200a (0.95±0.14) and miR-4652-3p (0.82±0.11) in cerebrospinal fluid of patients with good prognosis tuberculous meningitis were higher than those of patients with poor rognosis( 0.84±0.13, 0.73±0.10), and the differences were statistically significant (t=5.025, 5.262, all P<0.05), while the levels of cerebrospinal fluid adenosine deaminase, TNF-α, IL-23, LTB4, CRP and mRS scores in patients with good prognosis were lower than those in patients with poor prognosis (t=5.649, 7.721, 11.150, 9.455, 11.314, 14.407, all P<0.05). There was a positive correlation between the levels of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis (r=0.405, P<0.001). The levels of miR-200a and miR-4652-3p in cerebrospinal fluid were negatively correlated with LTB4, TNF-α, CRP, mRS scores, IL-23 and adenosine deaminase (r=-0.472, -0.466, -0.461, -0.435, -0.422, -0.419; -0.459, -0.531, -0.471, -0.417, -0.513, -0.408, all P ＜ 0.05). The AUC(95%CI) of miR-200a and miR-4652-3p to assess disease severity were 0.881 (0.825~0.923) and 0.878 (0.822~0.921), respectively. The AUC(95%CI) of both combination in assessing the severity of patients was 0.945 (0.902~0.973), which was higher than the single detection, and the differences were significant (Z=3.008, 2.960, all P=0.003). The AUC(95%CI) of poor prognosis patients evaluated by cerebrospinal fluid miR-200a and miR-4652-3p levels were 0.749 (0.681~0.809) and 0.756 (0.688~0.816), and the AUC of poor prognosis patients evaluated by both combination was 0.839 (0.778~0.889), which was higher than that measured separately, and the differences were significant (Z=2.994, 2.697, P=0.003, 0.007). Adenosine deaminase [OR(95%CI)：1.106(1.033~1.185)], miR-200a [OR(95%CI)：0.529(0.369~0.744)], miR-4652-3p [OR(95%CI)：0.471(0.310~0.715)], C-reactive protein [OR(95%CI)：4.423(1.459~13.412)], TNF-α [OR(95%CI)： 1.196(1.061~1.348)], IL-23 [OR(95%CI)：4.809(1.086~3.013)], and LTB4 [OR(95%CI)：1.327(1.064~1.655)] were influencing factors for poor prognosis in patients with tuberculous meningitis (all P<0.05). Conclusion The expressions of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis were down-regulated, and they were closely related to the severity and prognosis of the disease. The combination of the miR-200a and miR-4652-3p could better predict the severity and prognosis of tuberculous meningitis, which may have a certain clinical value.

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备注/Memo

备注/Memo:
作者简介：冷洁（1973-），女，本科，副主任医师，研究方向：结核性脑膜炎，E-mail：j3iw3e@163.com。
通讯作者：柳霞（1983-），女，本科，主治医生，研究方向：结核性脑膜炎，E-mail：liu11502158@163.com。
更新日期/Last Update: 2024-05-15