Department of Hematology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
Hematology. 2022 Dec;27(1):214-231. doi: 10.1080/16078454.2022.2029256.
Several studies scatteredly identified the myelodysplastic syndromes' transcriptomic profiles (MDS). However, the exploration of transcriptional signatures, key signalling pathways, and their association with prognosis and diagnosis in the integrated multiple datasets remains lacking.
We integrated the GSE4619, GSE19429, GSE30195, and GSE58831 microarray datasets of CD34 + cells for identifying the differentially expressed genes (DEGs) in the MDS. The series of bioinformatics methods are applied to identify the key hub genes, gene clusters, prognostic hub genes, and genes associated with diagnostic efficacy. Finally, we validated the expression differences of hub genes in the GSE114922 dataset.
We explored the DEGs related to gene ontology enrichment and KEGG pathways. We identified significant hub genes, including 168 upregulated hub genes (such as ) and 52 downregulated hub genes (such as and ) in the MDS. In addition, we identified six significant molecular complex detection (MCODE)-derived upregulated gene clusters and one downregulated gene cluster, respectively. Moreover, we found that the higher expression level of and and the lower expression level of and hub genes are significantly correlated with shorter survival times of MDS patients. Furthermore, the area value under the ROC curve (AUC) of and prognostic genes are more than 0.80, indicating that these genes could be effectively used for the diagnostic efficacy of MDS patients.
Identifying key hub genes and their association with the prognosis and diagnostic efficacy may provide substantial clues for the treatment and diagnosis of MDS patients.
有几项研究零散地鉴定了骨髓增生异常综合征的转录组谱(MDS)。然而,在综合多个数据集的情况下,对转录特征、关键信号通路及其与预后和诊断的关联的探索仍然缺乏。
我们整合了 GSE4619、GSE19429、GSE30195 和 GSE58831 的 CD34+细胞微阵列数据集,以鉴定 MDS 中的差异表达基因(DEGs)。应用一系列生物信息学方法来识别关键枢纽基因、基因簇、预后枢纽基因和与诊断疗效相关的基因。最后,我们验证了在 GSE114922 数据集中枢纽基因的表达差异。
我们探讨了与基因本体富集和 KEGG 通路相关的 DEGs。我们鉴定了 MDS 中显著的枢纽基因,包括 168 个上调的枢纽基因(如)和 52 个下调的枢纽基因(如和)。此外,我们分别鉴定了六个显著的分子复合物检测(MCODE)衍生的上调基因簇和一个下调基因簇。此外,我们发现,和基因的较高表达水平和和基因的较低表达水平与 MDS 患者较短的生存时间显著相关。此外,和预后基因的 ROC 曲线下面积值(AUC)大于 0.80,表明这些基因可有效用于 MDS 患者的诊断疗效。
鉴定关键枢纽基因及其与预后和诊断疗效的关联可能为 MDS 患者的治疗和诊断提供重要线索。