临床和实验医学杂志2024,Vol.23Issue(17) :1856-1861.DOI:10.3969/j.issn.1671-4695.2024.17.017

血清miR-499a、lnc RNA MALAT1在系统性红斑狼疮中表达及其与预后的关系

Expression of serum miR-499a and lnc RNA MALAT1 in systemic lupus erythematosus and their relationship with prognosis

赵琳琳 吴彩宇 代新华 何晶晶 程毅
临床和实验医学杂志2024,Vol.23Issue(17) :1856-1861.DOI:10.3969/j.issn.1671-4695.2024.17.017

血清miR-499a、lnc RNA MALAT1在系统性红斑狼疮中表达及其与预后的关系

Expression of serum miR-499a and lnc RNA MALAT1 in systemic lupus erythematosus and their relationship with prognosis

赵琳琳 1吴彩宇 1代新华 2何晶晶 1程毅1
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作者信息

  • 1. 北大荒集团总医院检验科 黑龙江 哈尔滨 150088
  • 2. 哈尔滨市道外区靖宇社区服务中心检验科 黑龙江 哈尔滨 150026
  • 折叠

摘要

目的 检测系统性红斑狼疮(SLE)患者血清微RNA(miRNA)-499a、长链非编码RNA(lnc RNA)肺癌转移相关转录本1(MALAT1)表达情况,并分析其与患者临床预后的关系.方法 选取2018年1月至2020年1月北大荒集团总医院收治的SLE患者152例作为SLE组进行回顾性研究,另选取同期无自身免疫性疾病的健康体检者155名作为对照组.根据SLE疾病活动指数评分(SLEDAI),将SLE患者分为静止期组(SLEDAI0~4分,n=43)、轻度活动期组(SLEDAI 5~9 分,n=41)、中度活动期组(SLEDAI 10~15 分,n=38)、重度活动期组(SLEDAI>15 分,n=30);根据是否发生肾损伤,将SLE患者分为非肾损伤组(n=71)与肾损伤组(n=81);以SLE患者血清miR-499a、lnc RNA MALAT1均值为标准,将SLE患者分为miR-499a高表达组(n=77)和miR-499a低表达组(n=75),lnc RNA MAL-AT1高表达组(n=79)和lnc RNA MALAT1低表达组(n=73);根据预后情况分为预后良好组(n=115)与预后不良组(n=37).比较SLE组与对照组、SLE患者不同分组(静止期组、轻度活动期组、中度活动期组、重度活动期组;非肾损伤与肾损伤组;预后良好与预后不良组;miR-499a高表达组和miR-499a低表达组;lnc RNA MALAT1高表达组和lnc RNA MALAT1低表达组)组间血清miR-499a、lnc RNA MALAT1表达差异;分析SLE患者血清miR-499a、lnc RNA MALAT1水平与临床病理特征的相关性;采用受试者操作特征(ROC)曲线分析血清miR-499a、lnc RNA MALAT1对SLE患者预后不良的预测价值.结果 SLE组患者血清miR-499a水平为0.24±0.07,低于对照组(1.01±0.18),lnc RNA MALAT1水平为3.75±0.82,高于对照组(1.02±0.19),差异均有统计学意义(P<0.05).血清miR-499a水平在静止期组(0.52±0.11)、轻度活动期组(0.22±0.08)、中度活动期组(0.10±0.04)、重度活动期组(0.05±0.01)依次降低,lnc RNA MALAT1水平在静止期组(2.35±0.71)、轻度活动期组(3.72±0.83)、中度活动期组(4.44±0.85)、重度活动期组(4.95±0.95)依次升高,差异均有统计学意义(P<0.05).预后不良组SLE患者血清miR-499a水平为0.11±0.02,低于预后良好组(0.29±0.09),lnc RNA MALAT1水平为5.20±0.85,高于预后良好组(3.28±0.79),差异均有统计学意义(P<0.05)o miR-499a高表达组抗dsDNA阳性、抗ANA阳性SLE患者占比均低于miR-499a低表达组,SLEDAI评分低于miR-499a低表达组,差异均有统计学意义(P<0.05);lnc RNA MALAT1高表达组抗dsDNA阳性、抗ANA阳性SLE患者中占比均高于lnc RNA MALAT1低表达组,SLEDAI评分高于lnc RNA MALAT1低表达组,差异均有统计学意义(P<0.05).SLE 患者血清 miR-499a、lnc RNA MALAT1 呈负相关(r=-0.836,P<0.05);血清 miR-499a水平预测SLE患者预后不良的曲线下面积(AUC)为0.815(灵敏度为86.5%,特异度为66.1%),血清lnc RNA MALAT1水平预测SLE患者预后不良的AUC为0.871(灵敏度为83.8%,特异度为74.8%).结论 SLE患者血清miR-499a降低、lnc RNA MALAT1水平升高,二者可能共同参与SLE的进展,有望作为SLE预后不良的生物学标志物.

Abstract

Objective To detect the expression of serum microRNA(miRNA)-499a and long noncoding RNA(lnc RNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)in patients with systemic lupus erythematosus(SLE),and to analyze their relationship with the clinical prognosis of patients.Methods A retrospective study was conducted on 152 SLE patients admitted to Beidahuang Group General Hospital from January 2018 to January 2020 as SLE group,and 155 healthy subjects without autoimmune diseases during the same period were se-lected as control group.According to SLE disease activity index(SLEDAI)score,SLE patients were divided into stationary phase group(SLEDAI 0-4 points,n=43),mild active phase group(SLEDAI 5-9 points,n=41),moderate active phase group(SLEDAI 10-15 points,n=38)and severe active phase group(SLEDAI>15 points,n=30).According to the occurrence of renal injury,SLE patients were divided into non-renal injury group(n=71)and renal injury group(n=81).SLE patients were divided into miR-499a high expression group(n=77)and miR-499a low expression group(n=75),lnc RNA MALAT1 high expression group(n=79)and lnc RNA MALAT1 low expression group(n=73)according to the mean value of serum miR-499a and lnc RNA MALAT1 in SLE patients.According to the prognosis,they were divided into the good prognosis group(n=115)and the poor prognosis group(n=37).The differences in the expression of serum miR-499a and lnc RNA MALAT1 among the groups were compared;the correlation between serum miR-499a and lnc RNA MALAT1 levels and clinicopath-ological characteristics in SLE patients was analyzed;the predictive value of serum miR-499a and lnc RNA MALAT1 for poor prognosis in SLE patients was analyzed by ROC curve.Results The serum miR-499a level in SLE group was 0.24±0.07,which was lower than that in the con-trol group(1.01±0.18),and the lnc RNA MALAT1 level was 3.75±0.82,which was higher than that in the control group(1.02±0.19),the differences were statistically significant(P<0.05).The levels of serum miR-499a in the stationary phase group(0.52±0.11),mild ac-tive phase group(0.22±0.08),moderate active phase group(0.10±0.04)and severe active phase group(0.05±0.01)decreased in turn,and the levels of lnc RNA MALAT1 in the stationary phase group(2.35±0.71),mild active phase group(3.72±0.83),moderate active phase group(4.44±0.85)and severe active phase group(4.95±0.95)increased in turn,the differences were statistically significant(P<0.05).The serum miR-499a level in SLE patients in poor prognosis group was 0.11±0.02,which was lower than that in the good prognosis group(0.29±0.09),the lnc RNA MALAT1 level was 5.20±0.85,which was higher than that in the good prognosis group(3.28±0.79),and the differences were statistically significant(P<0.05).The proportion of anti-dsDNA positive and anti-ANA positive SLE patients in the miR-499a high expression group was lower than that in the miR-499a low expression group,and the SLEDAI score was lower than that in the miR-499a low expression group,the differences were statistically significant(P<0.05);the proportion of anti-dsDNA positive and anti-ANA posi-tive SLE patients in the lnc RNA MALAT1 high expression group was higher than that in the lnc RNA MALAT1 low expression group,and the SLEDAI score was higher than that in the lnc RNA MALAT1 low expression group,the differences were statistically significant(P<0.05).The serum miR-499a and lnc RNA MALAT1 were negatively correlated in SLE patients(r=-0.836,P<0.05);the area under the curve(AUC)of serum miR-499a level predicting poor prognosis in SLE patients was 0.815(sensitivity of 86.5%,specificity of 66.1%),the AUC of serum lncRNA MALAT1 level for predicting poor prognosis in SLE patients was 0.871(sensitivity of 83.8%,specificity of 74.8%).Conclusion Ser-um miR-499a is decreased and lnc RNA MALAT1 level is increased in SLE patients,both of which may be involved in the progression of SLE,and are expected to be used as biomarkers for poor prognosis of SLE.

关键词

红斑狼疮,系统性/微RNAs/预后/miR-499a/lnc/RNA/MALAT1

Key words

Lupus erythematosus,systemic/MicroRNAs/Prognosis/miR-499a/lnc RNA MALAT1

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基金项目

2020年度黑龙江省卫生健康委科研项目(2020-214)

出版年

2024
临床和实验医学杂志
首都医科大学附属北京友谊医院

临床和实验医学杂志

CSTPCD
影响因子:1.504
ISSN:1671-4695
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