RRM2: a crosstalk gene for COVID-19 and intervertebral disc degeneration revealed by integrated WGCNA and machine learning

Abstract Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and COVID-19 has been reported to be an important risk factor for IDD. The aim of this study was to explore the molecular mechanisms underlying the effects of COVID-19 on IDD by identifying overlapping crosstalk genes associated with these two conditions. The identification of crosstalk genes between COVID-19 and IDD patients will have important clinical implications for early intervention in COVID-19 secondary IDD. Methods: The gene expression profiles of GSE157103 and GSE70362 were extracted from the GEO database. These profiles were then subjected to analysis using WGCNA, Lasso, and SVM-RFE, resulting in the identification of RRM2 as a crosstalk gene for both COVID-19 and IDD. Additionally, GSEA was employed to investigate the potential mechanisms by which RRM2 exerts its effects in disease. Furthermore, a relationship between RRM2 and immune cells was revealed through correlation analysis. Finally, independent external datasets (GSE171110 and GSE146904) were utilized to validate the diagnostic efficacy of RRM2. Results: The crosstalk gene RRM2 for both COVID-19 and IDD was identified through the application of WGCNA and machine learning algorithm. GSEA analysis further revealed that RRM2 participates in fatty acid metabolism, thereby promoting disc degeneration in IDD. Moreover, immunocorrelation analyses unveiled a negative regulatory role of RRM2 in CD56-bright natural killer cells and its induction of IDD disc degeneration. Conclusions: A crosstalk gene of COVID-19 and IDD, RRM2, was identified using WGCNA and machine learning algorithm, providing a new perspective for exploring possible mechanisms of secondary IDD in COVID-19.