Gene signature based on glycolysis is closely related to immune infiltration of patients with osteoarthritis

Background

Osteoarthritis (OA) is a degenerative arthritis with high levels of clinical heterogeneity. Aberrant metabolism such as shifting from oxidative phosphorylation to glycolysis is a response to changes in the inflammatory microenvironment of OA. Therefore, there is a pressing need to identify novel glycolysis regulators during OA progression.

Methods

We systematically studied glycolysis patterns mediated by 141 glycolysis regulators in 74 human synovial samples and discussed the characteristics of the immune microenvironment modified by glycolysis. The random forest (RF) method was applied to screen candidate hub glycolysis regulators in OA. RT-qPCR was performed to validate these key regulators. Then distinct glycolysis patterns were identified, and systematic correlation between these glycolysis patterns and immune cell infiltration was analyzed. The glycolysis score was constructed to quantify glycolysis patterns together with immune infiltration of individual OA patient.

Results

56 glycolysis-related differentially expressed genes (DEGs) were identified between OA and non-OA samples. STC1, VEGFA, KDELR3, DDIT4 and PGAM1 were selected as candidate genes to predict the probability of OA. Two glycolysis patterns in OA were identified. Glycolysis cluster A with higher glycolysis score was related to an inflamed phenotype.

Conclusions

Taken together, our results established a glycolysis-based genetic signature for OA, guided in-depth studies on the metabolic mechanism of OA, and facilitated to explore new clinical treatment strategies.