Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine

IN TRADITIONAL CHINESE MEDICINE (TCM), PATIENTS WITH RHEUMATOID ARTHRITIS (RA) CAN BE CLASSIFIED INTO TWO MAIN PATTERNS: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials.