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Abstract：
UNASSIGNED: Specific and sensitive diagnostic biomarkers for unstable angina (UA) are currently scarce. The diagnosis of UA usually relies on medical history and physician experience. This study aimed to analyze the expression profiles of microRNAs (miRNAs) in the serum extracellular vesicles (EVs) of UA patients, thus identifying potential diagnostic biomarkers of UA.
UNASSIGNED: This study is a prospective study and participants were recruited randomly. A total of 142 patients with UA, 8 with non-ST-elevation myocardial infarction (NSTEMI), and 8 with stable angina (SA) at Nanjing Hospital of Traditional Chinese Medicine Affiliated with Nanjing University of Chinese Medicine from January 2019 to February 2022 were recruited. Fifty-eight healthy volunteers (HVs) were recruited to the control group during the same period. Differentially expressed miRNAs in serum exosomes of UA patients were first identified by high-throughput sequencing, followed by verification via quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our findings aim to explore their diagnostic potentials in UA, and their biological functions, as well as the correlation between conventional biochemical indexes of UA.
UNASSIGNED: MiR-127, miR-150, and miR-145 were differentially expressed miRNAs in the serum EVs of 8 UA patients, 8 NSTEMI patients, 8 SA patients, and 8 HVs by high-throughput sequencing, which were downregulated in UA patients versus HVs. Moreover, the relative levels of differentially expressed miRNAs in the serum EVs of the remaining UA patients and HVs were measured by qRT-PCR. The area under the curve of miR-127, miR-150, and miR-145 in distinguishing UA patients from HVs was 0.872, 0.856, and 0.803, respectively. Notably, the area under the curve of the combination of the three differentially expressed miRNAs for diagnosing UA was 0.944. A GO analysis revealed that miR-127, miR-150, and miR-145 were mainly enriched in cell adhesion and migration, whereas KEGG pathway enrichment analysis showed that they were enriched in the PI3K-Akt, MAPK, and Hippo signaling pathways. Multivariable logistic regression analysis identified cardiac troponin I (cTnI) (P=0.0006), miR-127 (P=0.0001), miR-150 (P=0.0004), and miR-145 (P=0.0005) as independent risk factors for UA. Spearman\'s rank correlation test showed a significant correlation between cTnI and miR-127 (r=0.1988, P=0.0067).
UNASSIGNED: MiR-127, miR-150, and miR-145 in serum EVs are closely linked with UA and serve as novel diagnostic biomarkers.
UNASSIGNED: This study is a prospective study and participants were recruited randomly. A total of 142 patients with UA, 8 with non-ST-elevation myocardial infarction (NSTEMI), and 8 with stable angina (SA) at Nanjing Hospital of Traditional Chinese Medicine Affiliated with Nanjing University of Chinese Medicine from January 2019 to February 2022 were recruited. Fifty-eight healthy volunteers (HVs) were recruited to the control group during the same period. Differentially expressed miRNAs in serum exosomes of UA patients were first identified by high-throughput sequencing, followed by verification via quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our findings aim to explore their diagnostic potentials in UA, and their biological functions, as well as the correlation between conventional biochemical indexes of UA.
UNASSIGNED: MiR-127, miR-150, and miR-145 were differentially expressed miRNAs in the serum EVs of 8 UA patients, 8 NSTEMI patients, 8 SA patients, and 8 HVs by high-throughput sequencing, which were downregulated in UA patients versus HVs. Moreover, the relative levels of differentially expressed miRNAs in the serum EVs of the remaining UA patients and HVs were measured by qRT-PCR. The area under the curve of miR-127, miR-150, and miR-145 in distinguishing UA patients from HVs was 0.872, 0.856, and 0.803, respectively. Notably, the area under the curve of the combination of the three differentially expressed miRNAs for diagnosing UA was 0.944. A GO analysis revealed that miR-127, miR-150, and miR-145 were mainly enriched in cell adhesion and migration, whereas KEGG pathway enrichment analysis showed that they were enriched in the PI3K-Akt, MAPK, and Hippo signaling pathways. Multivariable logistic regression analysis identified cardiac troponin I (cTnI) (P=0.0006), miR-127 (P=0.0001), miR-150 (P=0.0004), and miR-145 (P=0.0005) as independent risk factors for UA. Spearman\'s rank correlation test showed a significant correlation between cTnI and miR-127 (r=0.1988, P=0.0067).
UNASSIGNED: MiR-127, miR-150, and miR-145 in serum EVs are closely linked with UA and serve as novel diagnostic biomarkers.
摘要：
■不稳定型心绞痛（UA）的特异性和敏感的诊断生物标志物目前很少。UA的诊断通常依赖于病史和医师经验。本研究旨在分析UA患者血清细胞外囊泡(EVs)中微小RNA(miRNA)的表达谱,从而确定UA的潜在诊断生物标志物。
■这项研究是一项前瞻性研究，参与者是随机招募的。共有142例UA患者，8例非ST段抬高型心肌梗死（NSTEMI），纳入2019年1月至2022年2月南京中医药大学附属南京中医院稳定型心绞痛（SA）患者8例。在同一时期招募了58名健康志愿者（HVs）进入对照组。首先通过高通量测序鉴定UA患者血清外泌体中差异表达的miRNA,然后通过定量逆转录聚合酶链反应（qRT-PCR）进行验证，和基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。我们的发现旨在探索他们在UA中的诊断潜力，以及它们的生物学功能，以及UA常规生化指标之间的相关性。
■MiR-127，miR-150和miR-145是8例UA患者血清EV中差异表达的miRNAs，8NSTEMI患者，8例SA患者，和8个HVs的高通量测序，与HV相比，UA患者的表达下调。此外，通过qRT-PCR测量其余UA患者和HV的血清EV中差异表达的miRNA的相对水平。miR-127、miR-150和miR-145在区分UA患者和HV中的曲线下面积分别为0.872、0.856和0.803。值得注意的是,用于诊断UA的三种差异表达的miRNA的组合的曲线下面积为0.944。GO分析显示miR-127、miR-150和miR-145主要富集在细胞粘附和迁移中。而KEGG途径富集分析表明，它们在PI3K-Akt中富集，MAPK,和河马信号通路。多变量logistic回归分析确定了心肌肌钙蛋白I（cTnI）（P=0.0006），miR-127(P=0.0001),miR-150(P=0.0004),miR-145(P=0.0005)为UA的独立危险因素。Spearman秩相关检验显示cTnI与miR-127呈显著相关(r=0.1988,P=0.0067)。
■血清EV中的MiR-127、miR-150和miR-145与UA密切相关，可作为新的诊断生物标志物。
■这项研究是一项前瞻性研究，参与者是随机招募的。共有142例UA患者，8例非ST段抬高型心肌梗死（NSTEMI），纳入2019年1月至2022年2月南京中医药大学附属南京中医院稳定型心绞痛（SA）患者8例。在同一时期招募了58名健康志愿者（HVs）进入对照组。首先通过高通量测序鉴定UA患者血清外泌体中差异表达的miRNA,然后通过定量逆转录聚合酶链反应（qRT-PCR）进行验证，和基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。我们的发现旨在探索他们在UA中的诊断潜力，以及它们的生物学功能，以及UA常规生化指标之间的相关性。
■MiR-127，miR-150和miR-145是8例UA患者血清EV中差异表达的miRNAs，8NSTEMI患者，8例SA患者，和8个HVs的高通量测序，与HV相比，UA患者的表达下调。此外，通过qRT-PCR测量其余UA患者和HV的血清EV中差异表达的miRNA的相对水平。miR-127、miR-150和miR-145在区分UA患者和HV中的曲线下面积分别为0.872、0.856和0.803。值得注意的是,用于诊断UA的三种差异表达的miRNA的组合的曲线下面积为0.944。GO分析显示miR-127、miR-150和miR-145主要富集在细胞粘附和迁移中。而KEGG途径富集分析表明，它们在PI3K-Akt中富集，MAPK,和河马信号通路。多变量logistic回归分析确定了心肌肌钙蛋白I（cTnI）（P=0.0006），miR-127(P=0.0001),miR-150(P=0.0004),miR-145(P=0.0005)为UA的独立危险因素。Spearman秩相关检验显示cTnI与miR-127呈显著相关(r=0.1988,P=0.0067)。
■血清EV中的MiR-127、miR-150和miR-145与UA密切相关，可作为新的诊断生物标志物。
