Screening protein predictive of response to tumor necrosis factor-α inhibitors treatment in rheumatoid arthritis by using iTRAQ technique and investigating its mechanism through signal pathway

ABSTRACT: Rheumatoid arthritis (RA) is a chronic and disabling disease. TNF-α inhibitors have demonstrated an outstanding performance in relieving joint inflammation and retarding bone erosion involved in RA. However, there is still about one-thirds of RA patients had a poor response to TNF α inhibitors. Currently the personalized biological treatment is the research hotspot. Recent studies focuses on exploring biomarkers predictive of drug response. The research methods such as genomics, transcriptomics, proteomics, metabolomics and immunocytology, have been applied, but they are not successfully integrated. The related studies in China are still at an initial stage, which necessitates an in-depth study in this area. Our preliminary study showed that TNF-α-308 gene polymorphisms existed in Chinese RA patients and PI3K/Akt signal pathway was ativated in proliferated synovial fibroblasts stimulated by TNF-α. Therefore, for the first attempt in China, we intend to screen for differential proteins by using iTRAQ technique in RA patients receiving anti-TNF-α therapy, and then verify the predictive effects of selected differential proteins from the upstream gene polymorphism to the downstream protein expression. We will also investigate the mechanisms of differential proteins involved in TNF-α related signal pathway by using in vitro gene transfer, siRNA interference, and RA animal models. Through our study we hope to discover a prediction protein with a domestic genetic background and finally establish a prediction system with Chinese characteristics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Rheumatoid Arthritis

SUBMITTER: Jian Chen  

LAB HEAD: Fen Li

PROVIDER: PXD010378 | Pride | 2022-02-15

REPOSITORIES: Pride