Department of Biotechnology and Genetic Engineering, Islamic University, Bangladesh.
Islamic University, Bangladesh.
Brief Bioinform. 2021 Nov 5;22(6). doi: 10.1093/bib/bbab197.
Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.
尽管常见健康状况与 2019 年冠状病毒病（COVID-19）的严重程度有关，但疾病修饰生物分子及其发病机制仍不清楚。本研究旨在通过基于网络的基因表达分析了解 COVID-19 对不同合并症的影响及其相互影响。使用共享失调的基因，我们确定了可能涉及它们共同发病机制的关键遗传决定因素和信号通路。COVID-19 表现出 93 个基因的显著上调和 15 个基因的下调。有趣的是，它与糖尿病（DM）、肺癌（LC）、心肌梗塞和高血压分别共享 28、17、6 和 7 个基因。重要的是，COVID-19 与 DM 和 LC 共享三个上调基因（即 MX2、IRF7 和 ADAM8）。相反，在 COVID-19 和 LC 中发现两个基因（即 PPARGC1A 和 METTL7A）下调。此外，大多数共享途径都与炎症反应有关。此外，我们确定了六个潜在的生物标志物和几个重要的调节因子，例如转录因子和 microRNAs，而显著的候选药物包括卡托普利、rilonacept 和 canakinumab。此外，预后分析表明，同时患有 COVID-19 可能导致 LC 患者的预后不良。本研究为 COVID-19 因合并症而进展提供了分子基础和途径。我们相信这些发现可能有助于进一步了解这些疾病之间的复杂关联，并为治疗开发提供依据。
