Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify geno...BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.展开更多
目的探讨慢性心功能不全患者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)微小RNA(microRNAs,miRNAs)差异表达与患者脑血管疾病的关系。方法这是一项对2019年1月至2022年4月期间从西安交通大学第一附属医院出院的274例...目的探讨慢性心功能不全患者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)微小RNA(microRNAs,miRNAs)差异表达与患者脑血管疾病的关系。方法这是一项对2019年1月至2022年4月期间从西安交通大学第一附属医院出院的274例失代偿性心力衰竭患者的观察性研究。对患者进行随访,直到2023年1月,观察患者缺血性脑血管事件情况。miRNA微阵列用于分析基线循环miRNAs水平。通过实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)验证差异表达的miRNAs。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析候选miRNAs对缺血性脑血管事件的预测价值。结果在随访期间[422(184~939)d],有24例患者发生缺血性脑血管事件。与未发生缺血性脑血管事件的患者相比,发生缺血性脑血管事件的患者服用抗凝剂、维生素K拮抗剂的患者比例显著降低,差异有统计学意义(P<0.05)。在两组基线PBMCs样本中分析了2549个miRNA的表达,并鉴定了20个差异表达的miRNAs(定义为FC>1.3和P<0.05)。qRT-PCR验证结果显示,与非缺血性脑血管事件患者相比,发生缺血性脑血管事件患者的PBMCs样本中hsa-miR-1273g-3p、hsa-miR-2861表达水平显著上调,hsa-miR-483-5p表达水平显著下调,差异有统计学意义(P<0.05)。ROC分析表明,hsa-miR-1273g-3p[曲线下面积(area under the curve,AUC)=0.745]预测心力衰竭患者缺血性脑血管事件的灵敏度和特异度分别为81%、56%,hsa-miR-2861(AUC=0.614)的灵敏度和特异度分别为76%、62%,hsa-miR-483-5p(AUC=0.821)的灵敏度和特异度分别为76%、80%。3种候选miRNAs联合的预测价值优于单独一种miRNA,其AUC、灵敏度和特异度分别为0.941、90%、98%。结论PBMCs中hsa-miR-1273g-3p、hsa-miR-2861表达水平上调和hsa-miR-483-5p表达水平下调可能与心力衰竭患者缺血性脑卒中风险增加有关。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
文摘BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.
文摘目的探讨慢性心功能不全患者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)微小RNA(microRNAs,miRNAs)差异表达与患者脑血管疾病的关系。方法这是一项对2019年1月至2022年4月期间从西安交通大学第一附属医院出院的274例失代偿性心力衰竭患者的观察性研究。对患者进行随访,直到2023年1月,观察患者缺血性脑血管事件情况。miRNA微阵列用于分析基线循环miRNAs水平。通过实时定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)验证差异表达的miRNAs。采用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析候选miRNAs对缺血性脑血管事件的预测价值。结果在随访期间[422(184~939)d],有24例患者发生缺血性脑血管事件。与未发生缺血性脑血管事件的患者相比,发生缺血性脑血管事件的患者服用抗凝剂、维生素K拮抗剂的患者比例显著降低,差异有统计学意义(P<0.05)。在两组基线PBMCs样本中分析了2549个miRNA的表达,并鉴定了20个差异表达的miRNAs(定义为FC>1.3和P<0.05)。qRT-PCR验证结果显示,与非缺血性脑血管事件患者相比,发生缺血性脑血管事件患者的PBMCs样本中hsa-miR-1273g-3p、hsa-miR-2861表达水平显著上调,hsa-miR-483-5p表达水平显著下调,差异有统计学意义(P<0.05)。ROC分析表明,hsa-miR-1273g-3p[曲线下面积(area under the curve,AUC)=0.745]预测心力衰竭患者缺血性脑血管事件的灵敏度和特异度分别为81%、56%,hsa-miR-2861(AUC=0.614)的灵敏度和特异度分别为76%、62%,hsa-miR-483-5p(AUC=0.821)的灵敏度和特异度分别为76%、80%。3种候选miRNAs联合的预测价值优于单独一种miRNA,其AUC、灵敏度和特异度分别为0.941、90%、98%。结论PBMCs中hsa-miR-1273g-3p、hsa-miR-2861表达水平上调和hsa-miR-483-5p表达水平下调可能与心力衰竭患者缺血性脑卒中风险增加有关。
