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造血干细胞移植受者的 microRNA 谱。

MicroRNA Profiles in Hematopoietic Stem Cell Transplant Recipients.

机构信息

Department of Adult Health and Nursing Systems, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA.

Bioinformatics Shared Resource, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.

出版信息

Biol Res Nurs. 2024 Oct;26(4):559-568. doi: 10.1177/10998004241257847. Epub 2024 May 31.

Abstract

Hematopoietic Stem Cell Transplant (HCT) is a potentially curative treatment for hematologic malignancies, including multiple myeloma. Biomarker investigation can guide identification of HCT recipients at-risk for poor outcomes. MicroRNAs (miRNAs) are a class of non-coding RNAs involved in the modulation and regulation of pathological processes and are emerging as prognostic and predictive biomarkers for multiple health conditions. This pilot study aimed to examine miRNA profiles associated with HCT-related risk factors and outcomes in patients undergoing autologous HCT. Patients eligible for autologous HCT were recruited and blood samples and HCT-related variables were collected. Differential expression analysis of miRNA was conducted on 24 patient samples to compare changes in miRNA profile in HCT eligible patients before and after transplant. Unsupervised clustering of differentially expressed ( .05) miRNAs pre- and post- HCT identified clusters of up- and down-regulated miRNAs. Four miRNAs (miR-125a-5p, miR-99b-5p, miR-382-5p, miR-145-5p) involved in hematopoiesis (differentiation of progenitor cells, granulocyte function, thrombopoiesis, and tumor suppression) were significantly downregulated post-HCT. Correlation analyses identified select miRNAs associated with risk factors (such as frailty, fatigue, cognitive decline) and quality of life pre- and post-HCT. Select miRNAs were correlated with platelet engraftment. Future studies should examine miRNA signatures in larger cohorts in association with HCT outcomes; and expand investigations in patients receiving allogeneic transplants. This will lead to identification of biomarkers for risk stratification of HCT recipients.

摘要

造血干细胞移植(HCT)是治疗血液系统恶性肿瘤(包括多发性骨髓瘤)的一种潜在治愈方法。生物标志物研究可以指导识别 HCT 受者中预后不良的风险。微小 RNA(miRNA)是一类非编码 RNA,参与病理过程的调节和调控,并且作为多种健康状况的预后和预测生物标志物而出现。本研究旨在探讨与 HCT 相关的风险因素和接受自体 HCT 的患者结局相关的 miRNA 谱。

入选接受自体 HCT 的患者,并采集血液样本和 HCT 相关变量。对 24 例患者样本进行 miRNA 差异表达分析,以比较 HCT 合格患者移植前后 miRNA 谱的变化。未监督聚类差异表达(.05)miRNA 前和 HCT 后鉴定上调和下调 miRNA 的聚类。四个 miRNA(miR-125a-5p、miR-99b-5p、miR-382-5p、miR-145-5p)参与造血(祖细胞分化、粒细胞功能、血小板生成和肿瘤抑制),HCT 后显著下调。相关性分析确定了与 HCT 前和后风险因素(如虚弱、疲劳、认知能力下降)和生活质量相关的选择 miRNA。选择 miRNA 与血小板植入相关。

未来的研究应该在更大的队列中检查与 HCT 结局相关的 miRNA 特征,并在接受同种异体移植的患者中扩大研究。这将导致鉴定 HCT 受者风险分层的生物标志物。

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