关键词: COVID-19 Co-pathogenesis Comorbidity KIRC Shared gene

Mesh : Humans COVID-19 / genetics SARS-CoV-2 / genetics Carcinoma, Renal Cell / genetics Reproducibility of Results Kidney Neoplasms / genetics Kidney

来  源:   DOI:10.7717/peerj.16927   PDF(Pubmed)

Abstract:
UNASSIGNED: COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated.
UNASSIGNED: We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases.
UNASSIGNED: We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan.
UNASSIGNED: This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.
摘要:
COVID-19是由SARS-CoV-2病毒引起的严重传染病,和以前的研究表明,肾肾透明细胞癌(KIRC)患者比普通人群更容易感染SARS-CoV-2。然而,它们的共同发病机制仍未完全阐明。
我们基于公共数据集获得了这两种疾病之间的共享基因,构建了一个由hub基因组成的预后风险模型,并使用内部和外部验证集验证了模型的准确性。我们进一步分析了预后风险模型的免疫景观,研究了枢纽基因的生物学功能,并使用qPCR检测其在肾细胞癌细胞中的表达。最后,我们从DSigDB和CellMiner数据库中搜索了与hub基因相关靶标相关的候选药物.
我们获得了KIRC和COVID-19之间的156个共享基因,并构建了由四个hub基因组成的预后风险模型。共有基因和hub基因在免疫相关功能和途径中高度富集。Hub基因在COVID-19和KIRC中显著过表达。ROC曲线,列线图,等。,表明了风险模型的可靠性和鲁棒性,这在内部和外部数据集中都得到了验证。此外,高风险组的患者表现出更高的免疫细胞比例,免疫检查点基因的高表达,和更活跃的免疫相关功能。最后,我们确定了有希望的COVID-19和KIRC药物,如依托泊苷,富维司坦,还有托普替康.
这项研究确定并验证了KIRC和COVID-19的四个共有基因。这些基因与免疫功能相关,可作为KIRC的潜在预后生物标志物。共享的途径和基因可能为进一步的机制研究和合并症的治疗提供新的见解。
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