A novel gene-expression-signature-based model for prediction of response to Tripterysium glycosides tablet for rheumatoid arthritis patients

Approximately 30% of rheumatoid arthritis (RA) patients treated with Tripterysium glycosides (TG) tablets fail to achieve clinical improvement, implying the essentiality of predictive biomarkers and tools. Herein, we aimed to identify possible biomarkers predictive of therapeutic effects of TG tablets in RA.

This hypothesis-generating study identified MX1, OASL, SPINK1, CRK, GRAPL and RNF2 as novel targets for RA therapeutic intervention, and the PLS model based on the expression levels of these candidate biomarkers may have a potential prognostic value in RA patients treated with TG tablets.

Gene expression profile in peripheral blood mononuclear cells obtained from a discovery cohort treated with TG tablets was detected by Affymetrix EG1.0 arrays. Then, a list of candidate gene biomarkers of response to TG tablets were identified by integrating differential expression data analysis and gene signal transduction network analysis. After that, a partial-least-squares (PLS) model based on the expression levels of the candidate gene biomarkers in RA patients was constructed and evaluated using a validation cohort.

Six candidate gene biomarkers (MX1, OASL, SPINK1, CRK, GRAPL and RNF2) were identified to be predictors of TG therapy. Following the construction of a PLS-based model using their expression levels in peripheral blood, both the 5-fold cross-validation and independent dataset validations showed the high predictive efficiency of this model, and demonstrated a distinguished improvement of the PLS-model based on six candidate gene biomarkers' expression in combination over the commonly used clinical and inflammatory parameters, as well as the gene biomarkers alone, in predicting RA patients' response to TG tablets. Conclusions: This hypothesis-generating study identified MX1, OASL, SPINK1, CRK, GRAPL and RNF2 as novel targets for RA therapeutic intervention, and the PLS model based on the expression levels of these candidate biomarkers may have a potential prognostic value in RA patients treated with TG tablets.