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骨髓增生异常肿瘤中 CD34+干细胞与原代骨髓细胞之间转录组谱的差异。

Discrepancy in transcriptomic profiling between CD34 + stem cells and primary bone marrow cells in myelodysplastic neoplasm.

机构信息

Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Translational Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; UNESP - Univ. Estadual Paulista, School of Medicine, Department of Pathology, Botucatu, São Paulo, Brazil.

出版信息

Leuk Res. 2023 Jun;129:107071. doi: 10.1016/j.leukres.2023.107071. Epub 2023 Mar 29.

DOI:10.1016/j.leukres.2023.107071
PMID:37004280
Abstract

Differentially expressed genes (DEGs) biomarkers can be used to help diagnose and monitor the disease, as well as to determine which treatments are most effective. So, given the complexity of Myelodysplastic neoplasm (MDS), it is difficult to determine the impact and disparities of DEGs between CD34 HSC (hematopoietic stem cells) or primary bone marrow cells (PBMC) in MDS pathogenesis, and therefore it remains largely unknown. Here, we performed an in-silico transcriptome analysis on CD34 HSC and PBMC from 1092 MDS patients analyzing the divergences between differential gene expression patterns in these two cell types as potential pathogenic biomarkers for MDS. Initially, we observed a difference of 7117 expressed transcripts between PBMC (n = 40,165) and CD34 +HSC (n = 33,048). Also, we identified that CD34 HSC and PBMC samples showed 240 and 2948 DEGs, respectively. In summary, we identified DEGs disparities in CD34 HSC and PBMC cell types. However, there was a certain similarity of the activated pathways in both cellular samples based on Gene Ontology and KEGG pathways enrichment analyses. Our results provide novel insights into novel DEGs biomarkers to MDS pathogenesis with clinical significance. AVAILABILITY OF DATA AND MATERIALS: All microarray databases were obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). To evaluate the biological function of differentially expressed genes, the DAVID (Database for Annotation, Visualization and Integrated Discovery tool was used) (https://david.ncifcrf.gov/).

摘要

差异表达基因(DEGs)生物标志物可用于帮助诊断和监测疾病,并确定哪些治疗方法最有效。因此,鉴于骨髓增生异常肿瘤(MDS)的复杂性,很难确定 DEGs 在 MDS 发病机制中在 CD34 HSC(造血干细胞)或原代骨髓细胞(PBMC)之间的影响和差异,因此这在很大程度上仍然未知。在这里,我们对来自 1092 名 MDS 患者的 CD34 HSC 和 PBMC 进行了计算机转录组分析,分析了这两种细胞类型之间差异基因表达模式的差异,作为 MDS 的潜在发病生物标志物。最初,我们观察到 PBMC(n=40165)和 CD34+HSC(n=33048)之间存在 7117 个差异表达的转录本。此外,我们确定 CD34 HSC 和 PBMC 样本分别显示 240 和 2948 个 DEGs。总之,我们鉴定了 CD34 HSC 和 PBMC 细胞类型之间的 DEGs 差异。然而,基于基因本体论和 KEGG 途径富集分析,两个细胞样本中的激活途径存在一定的相似性。我们的研究结果为 MDS 发病机制提供了新的见解,并具有临床意义。数据和材料的可及性:所有微阵列数据库均从基因表达综合数据库(https://www.ncbi.nlm.nih.gov/geo/)获得。为了评估差异表达基因的生物学功能,使用了 DAVID(Database for Annotation, Visualization and Integrated Discovery tool)(https://david.ncifcrf.gov/)。

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