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评估改变的微小RNA表达模式以预测新冠病毒疾病的严重程度。

Evaluation of altered miRNA expression pattern to predict COVID-19 severity.

作者信息

Srivastava Swati, Garg Iti, Singh Yamini, Meena Ramesh, Ghosh Nilanjana, Kumari Babita, Kumar Vinay, Eslavath Malleswara Rao, Singh Sayar, Dogra Vikas, Bargotya Mona, Bhattar Sonali, Gupta Utkarsh, Jain Shruti, Hussain Javid, Varshney Rajeev, Ganju Lilly

机构信息

Genomics Division, Defence Institute of Physiology and Allied Science (DIPAS), Lucknow Road, Timarpur, Delhi, 110054, India.

Pulmonary Medicine, Rajiv Gandhi Super Speciality Hospital (RGSSH), Delhi, India.

出版信息

Heliyon. 2023 Feb;9(2):e13388. doi: 10.1016/j.heliyon.2023.e13388. Epub 2023 Feb 1.

Abstract

Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, several biomarkers for COVID-19 have been validated however no specific and reliable biomarker for the prognosis of patients with COVID-19 infection exists. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n = 43) were enrolled and categorized in four study groups; Dead (n = 16), Severe (n = 10) and Moderate (n = 7) patients and healthy controls (n = 10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p ≤ 0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

摘要

2019年12月爆发的新冠疫情影响了全球数百万人。经过大量研究,已验证了几种新冠病毒的生物标志物,但尚无用于预测新冠病毒感染患者预后的特异性和可靠生物标志物。本研究旨在确定预测新冠严重程度的特异性生物标志物以及制定治疗方案的工具。招募了一小群受试者(n = 43),并将其分为四个研究组:死亡组(n = 16)、重症组(n = 10)、中度组(n = 7)和健康对照组(n = 10)。从外周血中分离出微小RNA后,在Illumina平台上进行了小RNA测序。miRNA的差异表达(将患者组与对照组比较)显示,有118个下调和103个上调的已知miRNA,其倍数变化(FC)表达≥2倍且p≤0.05。然后对差异表达的miRNA进行功能富集和网络分析。生物信息学分析得出31个miRNA(24个下调;7个上调)与新冠病毒显著相关,从ROC曲线获得的AUC>0.8。在之前的研究中,31个差异表达的miRNA中有17个与新冠病毒有关。三个miRNA,即hsa-miR-147b-5p和hsa-miR-107(下调)以及hsa-miR-1299(上调)在死亡患者中显示出显著的独特差异表达。另一组4个miRNA,即hsa-miR-224-5p(下调)以及hsa-miR-4659b-3p、hsa-miR-495-3p和hsa-miR-335-3p在重症患者中独特地差异上调。与健康对照组相比,三个miRNA家族的成员,即hsa-miR-20、hsa-miR-32和hsa-miR-548在所有患者组中均显著下调。因此,在新冠死亡、重症和中度患者中观察到了独特的miRNA表达谱。本研究提出了一组在新冠患者中鉴定出的miRNA,可作为预测新冠严重程度的潜在诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4141/9932743/e4d054e6949b/gr1.jpg

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