Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Houston, USA.
Mol Cancer. 2024 Oct 21;23(1):235. doi: 10.1186/s12943-024-02094-9.
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.
癌症患者更容易出现 COVID-19 病情恶化。开发能够识别 COVID-19 相关死亡风险较高的癌症患者的生物标志物，有助于确定哪些患者需要早期临床干预。与 COVID-19 侵袭性相关的基因组区域中包含的 miRNA 可能是临床结局的潜在生物标志物。
从德克萨斯大学 MD 安德森癌症中心的癌症患者（n=128）中采集 COVID-19 感染的血浆样本。从罗马尼亚蒂米什瓦拉市的市立临床急诊教学医院接种疫苗的健康个体（n=23）中采集血清样本。使用一种基于计算的定位克隆方法来识别 COVID-19 风险相关基因组区域（CORSAIRs）中 miRNA 的存在。通过 RT-qPCR 测量 miRNA 水平。
我们发现 miRNA 在 CORSAIR 中富集。血浆中 hsa-miR-150-5p 和 hsa-miR-93-5p 的水平较低与 COVID-19 相关的死亡风险增加相关。hsa-miR-92b-3p 的水平与 SARS-CoV-2 检测阳性相关。体外 TLR7/8 和 T 细胞受体（TCR）介导激活后，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。在接种辉瑞-BioNTech COVID-19 疫苗第二剂后 1 至 9 个月，健康个体的血清样本中测量到这三种 miRNA 的水平升高。SARS-CoV-2 感染人呼吸道上皮细胞会影响其分泌的细胞外囊泡中的 miRNA 水平。
miRNA 在 CORSAIR 中富集。血浆 miRNA 水平可能是预测癌症患者 COVID-19 相关死亡的潜在血液生物标志物。
