ABSTRACT
Objective To identify primary gout biomarkers. Methods Isobaric tags for relative and absolute quantitation (iTRAQ) technique combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen differentially expressed proteins, and to identify potential biomarkers by analysis of the biological process, cellular components, molecular functions, KEGG pathways and protein-protein interactions. Difference between two groups were measured byt test. Results We identified 95 differentially expressed proteins (50 up-regulated proteins and 45 down-regulated proteins, respectively), and 20 significant KEGG pathways. Among them, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase (ENOA), phosphoglycerate kinase (PGK1), glucose-6-phosphate isomerase (G6PI) and moesin might play a role in the pathogenesis of primary gout. Conclusion iTRAQ technology can detect differentially expressed proteins from proteome, provides a strong theoretical basis for the study of biomarkers and evidence for the mechanisms in primary gout. However, further studies are needed.
ABSTRACT
Objective To evaluate the clinical significance of serum level of vascular endothelial growth factor (VEGF),angiopoietin (Ang)-1 and Ang-2 in patients with rheumatoid arthritis (RA).Methods Serum levels of VEGF,Ang-1 and Ang-2 were measured with enzyme linked immunosorbent assay (ELISA).Twenty-one healthy subjects,24 osteoarthritis patients and 82 rheumatoid arthritis patients were included.We defined active and inactive group according to RA disease active score,while early active RA and late active RA group were defined on the basis of disease course.There were 28 early active patients,32 late active patients and 22 inactive patients with rheumatoid arthritis.At the same time 29 RA patients were examined with ultrasound.Synovial hypertrophy (US joint count SH,US index SH),synovial fluid(US joint count SF,US index SF),resistance index and power Doppler signal (US joint PD,TSS) were scored.The correlation was analyzed.We also detected the serum levels of VEGF,Ang-1,Ang-2,ESR,CRP and DAS28 in 25patients with active RA after 3 month regular treatment.We used one-way ANOVA to compare the differences between groups,and Wilcoxon test to compare the differences between before and after treatment.We analyzed the correlation with linear correlation or Spearman rank test.Results The serum level of VEGF [(1285 ±272) pg/ml],Ang-1 [(0.55±0.25)ng/ml] in patients with rheumatoid arthritis were higher than osteoarthritis patients [(934±80) pg/ml,(0.32±0.16) ng/ml] and normal controls [(565±115) pg/ml,(0.24±0.21) ng/ml],and the serum level of Ang-2 [(1.36±0.40) ng/ml] was higher than normal controls [(0.52±0.32) ng/ml].The serum level of VEGF [(1355±194) pg/ml] in early active patients was higher than late active patients [(1096±477) pg/ml] and inactive patients [(862±91) pg/ml].The serum level of Ang-1 in early active patients,late active patients and inactive patients with rheumatoid arthritis had no statistically significant differences.The serum level of Ang-2 in inactive patients [(2.0±2.0) ng/ml] was significantly higher than late active patients [0.9±0.8) ng/ml].The serum level of VEGF was positively correlated with US joint SH,US index SH,US joint PD,and TSS.The serum level of Ang-1 was positively correlated with US joint SH,US joint PD,and TSS.The serum level of VEGF and Ang-1 were negatively correlated with RI.The serum level of Ang-2 was not correlated with US joint SH,US index SH,US joint SF,US index SF,US joint PD,TSS and RI.In the active RA patients,the serum level of VEGF,Ang-1 and Ang-2 was positively correlated with each other.In the inactive RA patients,the serum level of VEGF,Ang-1 and Ang-2 was not correlated with each other.The serum level of VEGF and Ang-1 before treatment was slightly higher than that of after treatment,but the difference was not statistically significant.The serum level of Ang-2 after treatment was significantly higher than that before treatment.ESR,CRP and DAS28 of after treatment were lower than those before treatment.Conclusion The serum VEGF and Ang-1 level could be used as useful index to reflect RA synovial thickening and angiogenesis The serum level of Ang-2 could be used as one of the efficacy indices.They may influence each other,and they may be the key factors that mediate the onset and development of RA angiogenesis and synovial inflammation.