Identification and validation of BCL6 and VEGFA as biomarkers and ageing patterns correlating with immune infiltrates in OA progression

Abstract

AbstractOsteoarthritis (OA), the most common type of arthritis, is a complex biological response caused by cartilage wear and synovial inflammation that links biomechanics and inflammation. The progression of OA correlates with a rise in the number of senescent cells in multiple joint tissues. However, the mechanisms by which senescent cells and their involvement with immune infiltration promote OA progression are not fully understood. The gene expression profiles and clinical information of OA and healthy control synovial tissue samples were retrieved from the Gene Expression Omnibus database, and then differential analysis of senescence regulators between OA and normal samples was performed. The random forest (RF) was used to screen candidate senescence regulators to predict the occurrence of OA. The reverse transcription quantitative real-time PCR experiments at tissue’s level was performed to confirm these biomarkers. Moreover, two distinct senescence patterns were identified and systematic correlation between these senescence patterns and immune cell infiltration was analyzed. The senescence score and senescence gene clusters were constructed to quantify senescence patterns together with immune infiltration of individual OA patient. 73 senescence differentially expressed genes were identified between OA patients and normal controls. The RF method was utilized to build an OA risk model based on two senescence related genes: BCL6 and VEGFA. Next, two distinct aging patterns were determined in OA synovial samples. Most patients from senescence cluster A were further classified into gene cluster B and high senescence score group correlated with a non-inflamed phenotype, whereas senescence cluster B were classified into gene cluster A and low senescence score group correlated with an inflamed phenotype. Our study revealed that senescence played an important role in in OA synovial inflammation. Evaluating the senescence patterns of individuals with OA will contribute to enhancing our cognition of immune infiltration characterization, providing novel diagnostic and prognostic biomarkers, and guiding more effective immunotherapy strategies.