MicroRNA在COVID-19基因组风险区域富集，其血液水平与SARS-COV-2感染的癌症患者的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
影响因子:33.90000
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
摘要
癌症患者更容易受到19.19的激进进程。开发生物标志物，鉴定出患有共vid-19与19例相关死亡风险高风险的癌症患者可以帮助确定谁需要早期临床干预。与侵略性共vid-19的风险相关的基因组区域中的miRNA可以代表临床结果的潜在生物标志物。在德克萨斯大学MD Anderson癌症中心（n = 128）受到COVID-19的癌症患者（n = 128），收集了血质样品。从罗马尼亚蒂米索拉市的市政临床急诊教学医院中收集血清样本（n = 23）。使用一种计算机位置克隆方法来识别COVID-19风险相关的基因组区域上的miRNA的存在：COSARES（COVID-199风险相关的基因组区域）。通过RT-QPCR测量miRNA水平。我们发现miRNA富含海盗船。 HSA-MIR-150-5P和HSA-MIR-93-5P的血浆水平低与COVID-19相关死亡较高有关。 HSA-MIR-92B-3P的水平与SARS-COV-2测试阳性有关。体外TLR7/8/8和T细胞受体（TCR）介导的激活后，外周血单核细胞（PBMC）增加了HSA-MIR-150-5P，HSA-MIR-93-5P和HSA-MIR-92B-3P的分泌。在第二剂量pfizer-Biontech Covid-19疫苗后，在健康个体的血清样本中测量了这三个miRNA的水平。人类气道上皮细胞的SARS-COV-2感染会影响其分泌的细胞外囊泡内部的miRNA水平。血浆miRNA水平可以代表一种潜在的血液生物标志物，用于预测癌症患者的COVID-19相关死亡。
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.