Shervington Leroy, Darekar Ashish, Shaikh Murassa, Mathews Roshini, Shervington Amal
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK.
Stevenage Bioscience Catalyst, Stevenage, UK.
Biomark Insights. 2018 Sep 24;13:1177271918801005. doi: 10.1177/1177271918801005. eCollection 2018.
Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients.
Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA-untreated and MTX-treated cells were subjected to microarray analysis.
Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples.
The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with , and genes.
The data from this study suggest the use of , and gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX.
C反应蛋白升高通常是类风湿性关节炎(RA)的良好指标;然而,存在一些局限性会损害其特异性,因此迫切需要鉴定更可靠的诊断生物标志物以检测RA的早期阶段。此外,确定使用甲氨蝶呤(MTX)治疗RA的正确治疗生物标志物将极大地增加患者所获得的益处。
本研究选用原代正常人滑膜细胞人成纤维样滑膜细胞(HFLS)及其表型风湿性HFLS-RA细胞。对未处理和经MTX处理的HFLS-RA细胞进行微阵列分析。
微阵列数据鉴定出74个差异表达基因。这些基因与RA炎症途径进行比对,筛选出10个候选基因。研究了这10个基因的基因表达谱。计算倍数变化(FC)以确定样品的差异表达。
与HFLS细胞相比,10个候选基因的转录谱在HFLS-RA细胞中高度诱导。然而,用MTX处理HFLS-RA细胞后,这些基因的转录谱高度下调。在[具体基因1]、[具体基因2]和[具体基因3]基因中观察到HFLS与HFLS-RA(处理和未处理)之间最显著的表达FC差异。
本研究数据表明使用[具体基因1]、[具体基因2]和[具体基因3]基因表达谱作为潜在的诊断生物标志物。此外,这些基因谱有助于预测MTX的治疗效果。