New insights into genetic characteristics between multiple myeloma and COVID‐19: An integrative bioinformatics analysis of gene expression omnibus microarray and the cancer genome atlas data

Abstract

Background Multiple myeloma (MM) is a hematological malignancy. Coronavirus disease 2019 (COVID‐19) infection correlates with MM features. This study aimed to identify MM prognostic biomarkers with potential association with COVID‐19. Methods Differentially expressed genes (DEGs) in five MM data sets (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47552, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16558, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13591, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6477, and http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39754) with the same expression trends were screened out. Functional enrichment analysis and the protein‐protein interaction network were performed for all DEGs. Prognosis‐associated DEGs were screened using the stepwise Cox regression analysis in the cancer genome atlas (TCGA) MMRF‐CoMMpass cohort and the http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24080 data set. Prognosis‐associated DEGs associated with COVID‐19 infection in the http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164805 data set were also identified. Results A total of 98 DEGs with the same expression trends in five data sets were identified, and 83 DEGs were included in the protein‐protein interaction network. Cox regression analysis identified 16 DEGs were associated with MM prognosis in the TCGA cohort, and only the cytochrome c oxidase subunit 6C (COX6C) gene (HR = 1.717, 95% CI 1.231–2.428, p = .002) and the nucleotide‐binding oligomerization domain containing 2 (NOD2) gene (HR = 0.882, 95% CI 0.798–0.975, p = .014) were independent factors related to MM prognosis in the http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24080 data set. Both of them were downregulated in patients with mild COVID‐19 infection compared with controls but were upregulated in patients with severe COVID‐19 compared with patients with mild illness. Conclusions The NOD2 and COX6C genes might be used as prognostic biomarkers in MM. The two genes might be associated with the development of COVID‐19 infection.

Construction of a Prognosis Model of the Pyroptosis-Related Gene in Multiple Myeloma and Screening of Core Genes

“…Zmorzyński et al 23 found that the NOD2/CARD15 variant (3020insc) and PS6 polymorphism affect the occurrence and prognosis of MM. New insights into the genetic characteristics by Wang et al 24 between MM and COVID-19 showed that NOD2 and COX6C genes could be used as prognostic biomarkers for MM. These studies suggest that there is a correlation between pyroptosis-related genes and MM, which affects the occurrence and development of MM and may provide evidence for exploring the unknown mechanism of MM.…”

SARS-CoV-2/COVID-19 and its relationship with NOD2 and ubiquitination

“…In a study of multiple myeloma prognostic biomarkers and potential association with COVID-19, differentially expressed genes were identified, including NOD2 gene as an independent factor related to disease prognosis. NOD2 gene was downregulated in patients with mild COVID-19 infection compared with controls but was upregulated in patients with severe COVID-19 compared with patients with mild illness [ 42 ]. In a murine study, MDP treatment of Influenza A virus infected animals significantly reduced mortality, viral load, and pulmonary inflammation in a NOD2-dependent manner.…”

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

“…COX6C gene encodes component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. COX6C is differentially expressed in multiple myeloma (MM) and is associated with MM prognosis ( 44 ). Multiple myeloma (MM) is a malignant proliferation of plasma cells, with the coexistence of a monoclonal component (M-component) plus impairment of normal immunoglobulin production, which are associated with increased risk of viral and bacterial infections ( 45 ).…”