微RNA富集在COVID-19基因组风险区域，其血液水平与感染SARS-CoV-2的癌症患者COVID-19预后相关

MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2

Molecular Cancer

影响因子:33.9

分区:医学1区 Top / 生化与分子生物学1区肿瘤学1区

发表日期:2024 Oct 21

作者: Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A Calin

DOI: 10.1186/s12943-024-02094-9

摘要

癌症患者对COVID-19的侵袭性进程更为敏感。开发识别COVID-19相关死亡高风险癌症患者的生物标志物，有助于早期临床干预。宿主于与激进COVID-19风险相关的基因组区域的miRNAs可能代表潜在的临床结局生物标志物。本研究在德克萨斯大学MD安德森癌症中心收集了受COVID-19影响的癌症患者（N = 128）的血浆样本。在罗马尼亚蒂米什瓦拉市的市立临床急诊教学医院收集了接种疫苗的健康人群（n = 23）的血清样本。采用体外计算位置克隆方法（in silico）识别COVID-19风险相关基因组区域中的miRNAs：CORSAIRs（COvid-19 RiSk AssocIated genomic Regions）。通过RT-qPCR测定miRNA水平。我们发现miRNAs在CORSAIR中富集。血浆中hsa-miR-150-5p和hsa-miR-93-5p的低水平与COVID-19相关死亡率升高相关。hsa-miR-92b-3p的水平与SARS-CoV-2检测呈阳性相关。在体外TLR7/8和T细胞受体（TCR）激活后，外周血单核细胞（PBMC）分泌hsa-miR-150-5p、hsa-miR-93-5p和hsa-miR-92b-3p的增加。在接种第二剂辉瑞-BioNTech COVID-19疫苗后1至9个月，健康人血清样本中这三种miRNAs的水平升高。人类气道上皮细胞感染SARS-CoV-2会影响其分泌的胞外囊泡中的miRNA水平。miRNAs在CORSAIR中富集。血浆miRNA水平可以作为预测癌症患者COVID-19相关死亡的潜在血液生物标志物。

Abstract

Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR.We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles.MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.