Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study

Mohammad Soltani, Mohammad Jafar Sharifi, Parvin Khalilian, Mehran Sharifi, Pardis Nematollahi, Hooriyeh Shapourian, M. Hakemi
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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.  
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骨髓增生异常综合征 (MDS) 中热休克基因异常表达的潜在诊断价值:一项原发性观察队列研究
背景:骨髓增生异常综合征(MDS骨髓增生异常综合征(MDS)由无效造血和骨髓细胞学发育不良以及体细胞基因突变和染色体异常决定。越来越多的证据表明,NLRP3 炎症小体激活和细胞凋亡在 MDS 的发病机制中起着关键作用。虽然 MDS 可通过多种形态学和细胞遗传学检测进行诊断,但这些检测在实际应用中大多存在局限性或问题。材料与方法:在本研究中,我们评估了 MDS 患者骨髓标本中组成炎性体的基因(NLRP3、ASC 和 CASP1)的表达情况,并将其结果与其他白血病的结果进行了比较,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癌症患者(45 例)的抽吸样本。在提取 RNA 和合成 c.DNA 后,采用实时 PCR 方法(SYBER Green 检测法)测定候选转录本和看家转录本。使用 Kruskal-Wallis 对相对基因表达量进行比较,P 值小于 0.05 的差异被认为具有显著性。用隐性操作曲线(ROC)分析所有标记物的鉴别能力、临界值和曲线下面积(AUC)。结果 我们发现,与非 MDS 血液恶性肿瘤相比,Caspase-1 和 ASC 基因在 MDS 标本中的表达水平更高。Caspase-1和ASC的相对平均表达量分别为10.22和1.86,P值分别为0.001和0.019。ROC曲线分析显示,Caspase-1的AUC为0.739,p=0.0001;ASC的AUC为0.665,p=0.0139。结论我们的研究结果表明,Caspase-1和ASC基因表达水平可作为诊断MDS的潜在生物标志物。建议进行大样本量的前瞻性研究。
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