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Objective:This work aims to assess the distribution of peripheral blood monocyte subsets, the expression level of the functional markers in rheumatoid arthritis (RA) patients, and analyze the correlation between the above indexes and the onset of RA.Methods:Peripheral blood mononuclear cells were collected and isolated from 62 RA patients, 52 healthy control (HC) and 12 disease control group′s patients via density centrifugation. The enrolled patients were attended or underwent physical examination in East Hospital, Tongji University from June 2020 to December 2021. Monocytes could be classified into classical (CM), intermediate (IM) and non-classical (NCM). Then, the flow cytometry was performed to examine the distribution of monocyte subsets and the measure the expression level of human leukocyte antigen DR (HLA-DR), intracellular tumor necrosis factor α (TNF-α) in peripheral blood monocytes. The statistical methods in this study mainly include: Kruskal-Wallis H test, Chi-Square test, Mann-Whitney U test, Wilcoxon matched-pairs signed ranks test, Spearman correlation coefficient test and Logistic regression analysis. The diagnostic value of IM proportion in RA was analyzed by ROC curve. Results:The monocytes number and monocytes proportion in white blood cells were much higher in RA [0.40 (0.40, 0.50), 7.60% (5.97%, 8.53%)] and disease control [0.40 (0.40, 0.68), 8.20% (5.85%, 10.28%)] compared with HC [0.30 (0.30, 0.40), 5.80% (5.03%, 6.38%)] ( H=24.733, P<0.001; H=27.469, P<0.001). A statistic-significant difference was detected among the proportion of CM[85.49%(76.91%,89.21%),88.94%(86.36%,91.72%),90.26%(80.25%, 92.56%)],IM[11.65%(8.47%,17.89%),7.89%(5.36%,10.75%), 5.56%(4.17%, 8.27%)], NCM[2.22%(1.39%, 3.74%), 2.49%(1.74%, 4.66%), 5.13%(3.39%, 9.85%)] in RA group, HC group and disease control group ( H=11.389, P=0.003; H=20.815, P<0.001; H=10.640, P=0.005). The proportion of CM was lower in RA and the IM proportion was increased in RA( P=0.003; P=0.003). The intracellular TNF-α level of monocytes in all three groups revealed the trend that IM>NCM>CM. The intracellular TNF-α in IM of RA was positively associated with serum TNF-α ( r=0.376, P=0.041). The HLA-DR expression in IM subsets were higher than CM and NCM subsets in all RA,HC and disease control groups. The expression of HLA-DR of IM in RA group and disease control was higher than HC group [8 611.50 (6201.3, 9890.8), 10 295.0 (7 899.0, 13632.0), 6 278.00(4 057.8, 9522.0), H=10.495, P=0.005]. There were no correlations between the proportion of peripheral blood IM and clinical characteristics CRP ( r=0.119, P=0.359), RF ( r=0.204, P=0.112) and ESR ( r=0.153, P=0.236). Logistic regression analysis showed that the proportion of IM ( OR=1.169, 95% CI 1.003-1.363, P=0.046), CRP ( OR=1.277, 95% CI 1.000-1.631, P=0.050), RF ( OR=1.179, 95% CI 1.080-1.287, P<0.001) are positively correlated with RA onset. The area under ROC curve for diagnosis of RA with IM proportion was 0.687, and the 95% confidence interval was 0.590-0.784, P<0.001. Conclusions:The distribution of monocyte subsets in peripheral blood of RA patients is abnormal. The increase in the proportion of IM, the enhanced antigen-presenting ability, and the increased level of TNF-α secretion in RA patients may play an important role in the pathogenesis of RA.
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Rheumatoid arthritis (RA) is a chronic erosive arthritis. Early diagnosis, standardized treatment and regular monitoring of the disease will effectively mitigate disease progression and reduce the disability rate. Currently, traditional synthetic disease-modifying antirheumatic drugs (DMARDs) are used alone or in combination with new biological DMARDs or targeted synthetic DMARDS in the treatment of RA, resulting in effective remission in some refractory patients. However, the efficacy and toxicities of different treatments varies. With the development of proteomic and epigenetic technologies, some proteins, non-coding RNAs, and anti-drug antibodies (ADA) have been identified as potential markers for early diagnosis, concomitant diagnosis and disease assessment of RA. We summarized and analyzed the application prospects of novel RA diagnosis markers, including serum proteins, cell membrane proteins, non-coding RNAs, and ADA, with the aim of promoting the application of new markers that allow more precise diagnosis and treatment of RA.
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Objective To investigate the relationship between DNA topoisomerase Ⅱ α (TOP2A) gene expression and clinicopathological characteristics and its significance of prognostic evaluation for patients with bladder cancer.Methods Bladder cancer gene expression profile GSE13507 (n =165) and GSE31189 (n =52) were obtained.The expression profile and clinical information of patients with bladder cancer were retrospectively analyzed,and the survival analysis was made.Gene set enrichment analysis (GSEA) was conducted to explore the related pathways which were regulated by TOP2A.Results Compared with normal bladder tissues,TOP2A was upregnlated in bladder cancer tissues (5.823 ± 1.079 vs.4.820 ± 1.129),with a statistically significant difference (t =4.336,P ＜ 0.001).The TOP2A gene expression in patients with bladder cancer was correlated with the age of patients (x2 =5.926,P =0.015),sex (x2 =6.046,P =0.014),T staging (x2 =19.484,P ＜ 0.001),N staging (x2 =9.178,P =0.002),M staging (x2 =21.142,P ＜ 0.001),tumor grade (x2 =47.005,P ＜ 0.001),and progression (x2 =11.735,P =0.001),but it was not correlated with recurrence (x2 =0.808,P =0.369).Survival analysis showed that the specific survival rate in the 100 months of TOP2A gene high expression group and low expression group had a statistically significant difference (66.59％ vs.87.95％,x2 =15.820,P ＜ 0.001).The median overall survival time of TOP2A gene high expression group and low expression group were 51.77 months and 134.97 months respectively,with a statistically significant difference (x2 =11.280,P =0.008).The results of GSEA indicated that TOP2A could regulate gene sets related with several pathways like MYC-V1 signaling (P =0.035,FDR =0.132),MYC-V2 signaling (P =0.012,FDR =0.058),E2F signaling (P ＜ 0.001,FDR =0.006) and G2M checkpoint (P =0.006,FDR =0.044).Conclusion The TOP2A gene expression is closely related with clinicopathological characteristics of patients with bladder cancer.TOP2A may function as a potential marker of prognosis for patients with bladder cancer.