Department of Internal Medicine, Division of Hematology-Oncology, Korea University College of Medicine, Seoul, South Korea.
Department of Medical Science, Soonchunhyang University, Asan-si, South Korea.
PLoS One. 2024 Aug 23;19(8):e0306962. doi: 10.1371/journal.pone.0306962. eCollection 2024.
This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML.
BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples.
We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers.
Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.
本研究旨在利用急性髓系白血病（AML）患者骨髓（BM）抽吸物中的细胞外囊泡（EVs）建立具有临床意义的微小 RNA（miRNA）集，并鉴定与 AML 中这些 EV 衍生 miRNA 相互作用的基因。
在 AML 诊断时，从 32 例 AML 患者的 BM 抽吸物中采集 EVs。使用排阻层析法分离 EVs。在所有样本中鉴定出 965 种 EV 衍生 miRNA。
我们分析了有利（n = 10）和不利（n = 22）风险组中这些 EV 衍生 miRNA 的表达水平；在不利风险组中鉴定出 32 种差异表达的 EV 衍生 miRNA。使用来自癌症基因组图谱（TCGA）数据库的 AML 患者信息分析这些 miRNA 与风险分层和患者生存的相关性。在不利风险组中下调表达的 miRNA 中，hsa-miR-181b 和 hsa-miR-143 与不利风险和总生存期短相关。关于不利风险组中上调表达的 miRNA，hsa-miR-188 和 hsa-miR-501 与不利风险相关，并可预测不良生存。通过使用 TCGA 数据库进行 EV 衍生 miRNA-mRNA 网络分析，我们鉴定出 21 个可能是潜在不良预后生物标志物的 mRNAs。
总体而言，我们的研究结果表明 EV 衍生的 miRNA 可以作为 AML 风险分层和预后的生物标志物。此外，这些基于 EV 衍生 miRNA 的生物信息学分析可以帮助有效地鉴定具有潜在生物标志物的 mRNAs，类似于之前的细胞方法。
