Abstract:
Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.
摘要:
背景:骨髓增生异常综合征(MDS)是由无效的造血和骨髓细胞发育异常以及体细胞基因突变和染色体异常决定的。越来越多的证据表明,NLRP3炎性体激活和焦化性细胞死亡在MDS发病机制中的关键作用。虽然MDS可以通过各种形态学和细胞遗传学测试来诊断,这些测试中的大多数在实践中都有局限性或问题。材料和方法:在本研究中,我们评估了形成炎性体的基因的表达(NLRP3,ASC,和CASP1)在MDS患者的骨髓标本中,并将结果与其他白血病的结果进行比较,以评估其对MDS的诊断价值。这项观察性队列研究的主要样本来自骨髓增生异常综合征患者(27例)和非骨髓增生异常综合征血液系统癌症患者(45例)的抽吸样本。RNA提取和c.DNA合成后,通过实时PCR方法(SYBERGreen测定)测量候选转录本和管家转录本。使用Kruskal-Wallis比较了相对基因表达,p值小于0.05的差异被认为是显着的。辨别能力,切断,用隐性操作曲线(ROC)分析所有标记物的曲线下面积(AUC)。结果:我们发现,与非MDS血液恶性肿瘤相比,MDS标本中Caspase-1和ASC基因的表达水平更高。检测到Caspase-1和ASC的相对平均表达为10.22,p值为0.001,而1.86,p=0.019,分别。ROC曲线分析显示,对于Caspase-1,AUC为0.739,p=0.0001,对于ASC与MDS区分,AUC为0.665,p=0.0139。结论:我们的结果表明Caspase-1和ASC基因表达水平可作为MDS诊断的潜在生物标志物。建议进行大量样本的前瞻性研究。