Uncovering biomarkers for potential therapeutic targeting for COVID-19-related acute kidney injury: A bioinformatic approach

Abstract

ABSTRACT Objective: The Coronavirus Disease 2019 (COVID-19) is a recently-emerging infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), posing a significant threat to public health around the world. In patients with COVID-19, acute kidney injury (AKI) is a common complication associated with poor prognoses. We analyzed co-expressed genes to explore relationships between SARS-CoV2 infection and AKI, and revealed potential biomarkers and therapeutic targets of the COVID-19-associated AKI (COVID-19-AKI). Methods: We utilized the GSE147507 and GSE139061 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in SARS-CoV-2 infection and AKI, respectively. This was followed by analyzing protein-protein interaction networks, Gene Ontology, and pathway enrichment to uncover the relationship between DEGs. DEGs in common (co-DEGs), as well as corresponding interactive transcription factors (TFs) and microRNAs, were identified from the above results, followed by drug molecules uncovered for managing COVID-19-AKI. Aims: To reveal potential biomarkers and therapeutic targets for COVID-19-AKI by bioinformatic approach. Results: We discovered 345 DEGs in the lung and 310 DEGs AKI samples from COVID-19 patients, respectively. IFIT1, ISG15, MX1, IFIT3, and IFIT2 were involved in SARS-CoV-2 pulmonary infection, while hub genes such as RPL23, EIF4A1, RPS8, RPL13, and UPF2 were associated with AKI. We further derived co-DEGs including ERRFI1, KLK10, NR4A1, PODXL, RASGEF1C, RNU11, SNORA12, SNORA74B, and VTRNA1-1 coupled with their predicted transcription factors, including BACH2, HNF4A, MYC, and microRNAs containing miR-637, miR-542-3p, and miR-224. These targets may correlate with COVID-19-AKI, for which candidate drugs were identified. Conclusions: ERRFI1, KLK10, NR4A1, PODXL, RASGEF1C, RNU11, SNORA12, SNORA74B, and VTRNA1-1 may be associated with COVID-19-AKI and serve as novel markers.