Rheumatoid arthritis with deficiency pattern in traditional chinese medicine shows correlation with cold and hot patterns in gene expression profiles

Abstract

In our precious study, the correlation between cold and hot patterns in traditional Chinese medicine (TCM) and gene expression profiles in rheumatoid arthritis (RA) has been explored. Based on TCM theory, deficiency pattern is another key pattern diagnosis among RA patients, which leads to a specific treatment principle in clinical management. Therefore, a further analysis was performed aiming at exploring the characteristic gene expression profile of deficiency pattern and its correlation with cold and hot patterns in RA patients by bioinformatics analysis approach based on gene expression profiles data detected with microarray technology. The TCM deficiency pattern-related genes network comprises 7 significantly, highly connected regions which are mainly involved in protein transcription processes, protein ubiquitination, toll-like receptor activated NF- κ B regulated gene transcription and apoptosis, RNA clipping, NF- κ B signal, nucleotide metabolism-related apoptosis, and immune response processes. Toll-like receptor activated NF- κ B regulated gene transcription and apoptosis pathways are potential specific pathways related to TCM deficiency patterns in RA patients; TCM deficiency pattern is probably related to immune response. Network analysis can be used as a powerful tool for detecting the characteristic mechanism related to specific TCM pattern and the correlations between different patterns.

Figure 1

Protein-protein interaction (PPI) network for deficiency pattern-related genes. Cycles represent nodes. All edges represent interactions between the nodes. The green nodes represent cold pattern-related molecules; plum stands for hot pattern-related molecules; light blue stands for deficiency pattern; yellow stands for both cold and hot patterns; bluish green stands for both cold and deficiency patterns; deep blue stands for both hot and deficiency patterns; dark blue stands for cold, hot, and deficiency patterns.

Figure 2

The subnetworks made up of highly connected regions and functions of the nodes in TCM deficiency pattern-related genes. Cycles represent nodes. All edges represent interactions between the nodes. Clusters with score >2 were considered to be significant (it represents the log of the probability that the network was found by chance).

Figure 3

(a) Central PPI subnetwork related to deficiency pattern in RA. (b) PPI network from combined modules of cold, hot, and deficiency patterns-related genes. Cycles represent nodes. All edges represent interactions between the nodes. The green nodes represent cold pattern-related molecules; plum stands for hot pattern-related molecules; light blue stands for deficiency pattern; yellow stands for both cold and hot patterns; bluish green stands for both cold and deficiency patterns; deep blue stands for both hot and deficiency patterns; dark blue stands for cold, hot, and deficiency patterns.

Figure 4

Correlations and characteristics among TCM deficiency, cold, and hot patterns in RA concerning pathways and clinical manifestations. Blue square denotes cold pattern, red square represents hot pattern, and yellow square indicates deficiency pattern.