血清LncRNA HCG11及miR-26b-5p与急性缺血性脑卒中患者脑梗死面积及功能预后的相关性

Correlation Between Berum LncRNA HCG11， miR-26b-5p Levels and Infarction Area and Functional Prognosis in Patients with Acute Ischemic Stroke

摘要

目的 研究急性缺血性脑卒中患者血清长链非编码RNA人类白细胞抗原复合物组11（long non coding RNA human leukocyte antigen complex group 11， LncRNA HCG11）及微小核糖核酸-26b-5p（microRNA-26b-5p， miR-26b-5p）水平与脑梗死面积及功能预后的相关性。 方法 选取2021年1月至2022年12月本院收治的急性缺血性脑卒中患者106例，根据梗死面积将其分为小面积组、中面积组和大面积组，随访1年后根据改良Rankin量表（modified Rankin Scale， mRS）分为预后良好组和预后不良组。采用qRT-PCR检测LncRNA HCG11，miR-26b-5p相对表达量；采用Logistic回归分析影响患者预后的因素；绘制受试者工作特征（receiver operating characteristic， ROC）曲线分析LncRNA HCG11和miR-26b-5p对患者梗死面积的诊断及对预后的预测价值。采用Spearman相关分析LncRNA HCG11、miR-26b-5p与梗死面积及美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale， NHISS）的相关性。 结果 急性缺血性脑卒中大面积梗死患者的LncRNA HCG11水平升高，miR-26b-5p水平降低（P < 0.05）；与预后良好患者相比，预后不良患者的LncRNA HCG11水平升高，miR-26b-5p水平降低（P < 0.05）；不同梗死面积患者高血压史、高血脂史以及NHISS评分、C-反应蛋白（C-reactive protein， CRP）之间比较，差异具有统计学意义（P < 0.05）；LncRNA HCG11与梗死面积及NHISS均呈正相关（r_梗死面积= 0.553，P_梗死面积< 0.001；r_NHISS = 0.462，P_NHISS< 0.001），miR-26b-5p与梗死面积及NHISS均呈负相关（r'_梗死面积= -0.534，P'_梗死面积< 0.001；r'_NHISS = -0.447，P'_NHISS< 0.001）；miR-26b-5p为影响患者预后不良的保护因素，高血压史、NHISS评分、CRP和LncRNA HCG11为患者预后不良的影响因素（P < 0.05）；LncRNA HCG11和miR-26b-5p及联合诊断患者梗死面积优于单独指标诊断（Z_{LncRNA HCG11} = 3.049，P_{LncRNA HCG11} = 0.002；Z_miR-26b-5p = 2.657，P_miR-26b-5p = 0.008，AUC = 0.937）；且LncRNA HCG11+miR-26b-5p对患者预后的预测能力显著优于LncRNA HCG11、miR-26b-5p、CRP、NHISS单独指标（Z_{LncRNA HCG11} = 2.207，P_{LncRNA HCG11}= 0.027；Z_miR-26b-5p= 2.080，P_miR-26b-5p= 0.038；Z_CRP = 2.341，P_CRP = 0.019；Z_NHISS = 2.093，P_NHISS= 0.036，AUC = 0.892）；LncRNA HCG11与miR-26b-5p呈负相关（r = -0.425，P < 0.05）。 结论 急性缺血性脑卒中患者血清LncRNA HCG11水平升高，miR-26b-5p水平降低，均为患者脑梗死面积及功能预后的影响因素，对患者脑梗死面积及功能预后具有一定的诊断及预测价值。

Abstract

Objective To study and analyze the correlation between serum long non coding RNA human leukocyte antigen complex group 11 （LncRNA HCG11） and microRNA（miR）-26b-5p levels with cerebral infarction area and functional prognosis in patients with acute ischemic stroke. Methods From January 2021 to December 2022， 106 patients with acute ischemic stroke admitted to our hospital were collected. They were separated into the small area group， the medium area group， and the large area group based on the infarct size. After one year of follow-up， patients were categorized into a good prognosis group and a poor prognosis group based on the modified Rankin Scale （mRS）. QRT-PCR was applied to detect the relative expression levels of LncRNA HCG11 and miR-26b-5p. Logistic regression was applied to analyze the factors that affected the infarct size and prognosis of patients. Receiver operating characteristic （ROC） curve was plotted to analyze the diagnostic value of LncRNA HCG11， miR-26b-5p for infarct size and prognosis. Spearman correlation was used to analyze the correlation of LncRNA HCG11 and miR-26b-5p with infarct size and National Institutes of Health Stroke Scale （NHISS）. Results The level of LncRNA HCG11 increased and the level of miR-26b-5p decreased in patients with large area acute ischemic stroke infarction （P < 0.05）. Compared with patients with good prognosis， patients with poor prognosis had higher level of LncRNA HCG11 and lower level of miR-26b-5p （P < 0.05）. There were statistically significant differences （P < 0.05） in the history of hypertension， hyperlipidemia， NHISS scores， and C-reactive protein （CRP） levels among patients with different infarct sizes. LncRNA HCG11 was positively correlated with both infarct size and NHISS （r_梗死面积 = 0.553， r_NHISS =0.462， P < 0.001）， and miR-26b-5p was negatively correlated with both infarct size and NHISS （r'_梗死面积 = -0.534， P'_梗死面积< 0.001；r'_NHISS = -0.447， P'_NHISS< 0.001）. MiR-26b-5p was a protective factor that poor prognosis in patients. Hypertension history， NHISS score， CRP， and LncRNA HCG11 were risk factors for poor prognosis in patients （P < 0.05）. LncRNA HCG11 and miR-26b-5p and the combined diagnosis of infarct size in patients was superior to the diagnosis of separate indicators （Z_{LncRNA HCG11} = 3.049，P_{LncRNA HCG11} = 0.002；Z_miR-26b-5p = 2.657，P_miR-26b-5p = 0.008，AUC=0.937）. LncRNA HCG11+miR-26b-5p predicted patient prognosis significantly better than LncRNA HCG11， miR-26b-5p， CRP， NHISS alone （Z_{LncRNA HCG11} = 2.207， P_{LncRNA HCG11}= 0.027； Z_miR-26b-5p= 2.080， P_miR-26b-5p= 0.038； Z_CRP = 2.341， P_CRP = 0.019； Z_NHISS = 2.093， P_NHISS= 0.036， AUC=0.892）. LncRNA HCG11 was negatively correlated with miR-26b-5p （r= -0.425， P<0.05）. Conclusion Serum LncRNA HCG11 level increased and miR-26b-5p level decreased in patients with acute ischemic stroke， both of which were influencing factors on cerebral infarct size and functional prognosis， and showed certain diagnostic and predictive value for cerebral infarct size and functional prognosis.

关键词

急性缺血性脑卒中 / 长链非编码RNA人类白细胞抗原复合物组11 / 微小核糖核酸-26b-5p / 脑梗死面积 / 预后 / 相关性

Key words

Acute ischemic stroke / Long non coding RNA human leukocyte antigen complex group 11 / MicroRNA-26b-5p / Cerebral infarction area / Prognosis / Correlation

基金资助

河南省科技发展计划项目(192102310349)

南阳市科技攻关项目(KJGG2018082)