血浆长链非编码RNA浆细胞瘤变异易位基因1、微小RNA-143-3p表达水平与类风湿关节炎患者疾病活动度及预后的相关性分析

Correlations of the expression levels of plasma long non-coding RNA plasmacytoma variant translocation 1 and microRNA-143-3p with disease activity and prognosis in patients with rheumatoid arthritis

  • 摘要:
    目的 分析血浆长链非编码RNA浆细胞瘤变异易位基因1(LncRNA PVT1)、微小RNA-143-3p(miR-143-3p)表达水平与类风湿关节炎(RA)患者疾病活动度及预后的相关性。
    方法 选取本院2021年4月—2023年4月收治的RA患者129例为疾病组,依据28个关节疾病活动度评分(DAS28)将患者分为疾病稳定组(n=28)、轻度活动组(n=42)、中度活动组(n=35)、重度活动组(n=24); 根据治疗6个月的预后情况将其分为预后良好组(n=88)、预后不良组(n=41), 另选取同期在本院体检的110例健康者为对照组。采用实时荧光定量聚合酶链式反应(qRT-PCR)检测血浆LncRNA PVT1、miR-143-3p表达水平;通过Target Scan Human网站预测LncRNA PVT1、miR-143-3p的靶向关系;采用多因素Logistic回归分析探讨RA患者预后的影响因素; 绘制受试者工作特征(ROC)曲线分析血浆LncRNA PVT1、miR-143-3p对RA患者预后的预测价值。
    结果 疾病组血浆LncRNA PVT1水平高于对照组,血浆miR-143-3p水平低于对照组,差异有统计学意义(P < 0.05)。重度活动组、中度活动组、轻度活动组、疾病稳定组血浆LncRNA PVT1水平依次降低,血浆miR-143-3p水平依次升高,差异有统计学意义(P < 0.05)。预后不良组人类白细胞抗原-DR4(HLA-DR4)阳性占比、DAS28、血浆LncRNA PVT1表达水平高于预后良好组,血浆miR-143-3p水平低于预后良好组,差异有统计学意义(P < 0.05)。血浆LncRNA PVT1、miR-143-3p表达、HLA-DR4阳性、DAS28为RA患者预后的影响因素(P < 0.05)。LncRNA PVT1与miR-143-3p有靶向结合位点,且两者呈负相关(P < 0.05)。血浆LncRNA PVT1与miR-143-3p联合预测RA患者预后的曲线下面积(AUC)为0.914, 优于LncRNA PVT1、miR-143-3p单独诊断(Z=2.159, P=0.031; Z=2.108, P=0.035), 联合诊断的敏感度、特异度分别为95.12%、78.41%。
    结论 血浆LncRNA PVT1水平随RA疾病活动度的增加而逐渐升高,而血浆miR-143-3p水平随疾病活动度的增加而逐渐降低,二者联合检测对RA患者预后有较高的预测价值。

     

    Abstract:
    Objective To investigate the correlations of the expression levels of plasma long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) and microRNA-143-3p (miR-143-3p) with disease activity and prognosis in patients with rheumatoid arthritis (RA).
    Methods A total of 129 RA patients admitted to our hospital from April 2021 to April 2023 were selected as disease group. According to the 28-joint disease activity scores (DAS28), the patients were divided into stable disease group (n=28), mildly active group (n=42), moderately active group (n=35), and severely active group (n=24). According to the prognosis of the patients after 6 months of treatment, they were divided into good prognosis group (n=88) and poor prognosis group (n=41), and 110 healthy people who underwent physical examinations in our hospital during the same period were included as control group. The expression levels of plasma LncRNA PVT1 and miR-143-3p were detected using quantitative real-time fluorescent polymerase chain reaction (qRT-PCR). The targeting relationship between LncRNA PVT1 and miR-143-3p was predicted using the Target Scan Human website. Multivariate Logistic regression analysis was conducted to explore the factors influencing the prognosis of RA patients. Receiver operating characteristic (ROC) curve was performed to assess the predictive value of plasma LncRNA PVT1 and miR-143-3p for the prognosis of RA patients.
    Results The plasma LncRNA PVT1 level in the disease group was higher than that in the control group, while the plasma miR-143-3p level was lower (P < 0.05). The plasma LncRNA PVT1 levels decreased sequentially in the severe activity, moderate activity, mild activity, and disease stable groups, while the plasma miR-143-3p levels increased sequentially (P < 0.05).The proportion of patients positive for human leukocyte antigen-DR4 (HLA-DR4), DAS28, and plasma LncRNA PVT1 expression level were higher in the poor prognosis group than in the good prognosis group, while the plasma miR-143-3p level was lower (P < 0.05). Plasma LncRNA PVT1, miR-143-3p expression, HLA-DR4 positivity, and DAS28 were factors influencing the prognosis of RA patients (P < 0.05). LncRNA PVT1 and miR-143-3p had targeted binding sites, and there was a negative correlation between them (P < 0.05). The area under the curve (AUC) for the combined prediction of plasma LncRNA PVT1 and miR-143-3p for prognosis of RA patients was 0.914, which was superior to the individual diagnosis of LncRNA PVT1 or miR-143-3p (Z=2.159, P=0.031; Z=2.108, P=0.035). The sensitivity and specificity of the combined diagnosis were 95.12% and 78.41%, respectively.
    Conclusion The plasma LncRNA PVT1 level gradually increases, while the plasma miR-143-3p level gradually decreases with increasing RA disease activity. The combined detection of the two biomarkers has high predictive value for the prognosis of RA patients.

     

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