Identification of Key Genes Related to Immune Cells in Patients with COVID-19 Via Integrated Bioinformatics-Based Analysis

Abstract

COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis. The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms. There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signaling pathway. As much as 357 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signaling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI 0.920–0.988), 0.941(95% CI 0.892–0.980), and 0.929 (95% CI 0.880–0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells. Our study discovered that CDC25A, PDCD6, and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10528-023-10400-1.

Multifaceted roles of PDCD6 both within and outside the cell

“…This work suggests that PDCD6 functions as a negative regulator of cytosolic DNA-induced innate immune responses. Additionally, a recent study discovered that PDCD6 is significantly differentially expressed in normal individuals and COVID-19 patients, so it may be a diagnostic marker for COVID-19 (Chen et al, 2023).…”

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“…CDC25A (Cell Division Cycle-25A) plays a crucial role in the cell cycle and apoptosis by dephosphorylating its substrates (69). mRNA expression of CDC25A has been reported to be downregulated in aging skeletal muscle (70) and up-regulated in COVID-19 (71). In COVID-19, CDC25A has been found to be closely associated with immune cell infiltration such as plasma cells, macrophages, T cells, dendritic cells and NK cells, and plays an important role in disease progression as a biomarker for COVID-19 diagnosis (71,72).…”

“…mRNA expression of CDC25A has been reported to be downregulated in aging skeletal muscle (70) and up-regulated in COVID-19 (71). In COVID-19, CDC25A has been found to be closely associated with immune cell infiltration such as plasma cells, macrophages, T cells, dendritic cells and NK cells, and plays an important role in disease progression as a biomarker for COVID-19 diagnosis (71,72). It has been demonstrated that MYBL2 and BCL6 are significantly upregulated in SARS-CoV-2 infected patients (73,74).…”

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“…CDC25A (Cell Division Cycle-25A) plays a crucial role in the cell cycle and apoptosis by dephosphorylating its substrates (69). mRNA expression of CDC25A has been reported to be downregulated in aging skeletal muscle (70) and up-regulated in COVID-19 (71). In COVID-19, CDC25A has been found to be closely associated with immune cell infiltration such as plasma cells, macrophages, T cells, dendritic cells and NK cells, and plays an important role in disease progression as a biomarker for COVID-19 diagnosis (71,72).…”

“…mRNA expression of CDC25A has been reported to be downregulated in aging skeletal muscle (70) and up-regulated in COVID-19 (71). In COVID-19, CDC25A has been found to be closely associated with immune cell infiltration such as plasma cells, macrophages, T cells, dendritic cells and NK cells, and plays an important role in disease progression as a biomarker for COVID-19 diagnosis (71,72). It has been demonstrated that MYBL2 and BCL6 are significantly upregulated in SARS-CoV-2 infected patients (73,74).…”