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开发基于 DNA 甲基化的急性髓系白血病预后生物标志物。

Developing DNA methylation-based prognostic biomarkers of acute myeloid leukemia.

机构信息

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, China.

出版信息

J Cell Biochem. 2018 Dec;119(12):10041-10050. doi: 10.1002/jcb.27336. Epub 2018 Sep 1.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous clonal neoplasm characterized by complex genomic alterations. The incidence of AML increases with age, and most cases experience serious illness and poor prognosis. To explore the relationship between abnormal DNA methylation and the occurrence and development of AML based on the Gene Expression Database (GEO), this study extracted data related to methylation in AML and identified a methylated CpG site that was significantly different in terms of expression and distribution between the primary cells of AML patients, and hematopoietic stem/progenitor cells from normal bone marrow. To further investigate the differences caused by the dysfunction of methylation sites, bioinformatics analysis was used to screen methylation-related biomarkers, and the potential prognostic genes were selected by univariate and multivariate Cox proportional hazards regressions. Finally, five independent prognostic indicators were identified. In addition, these results provide new insight into the molecular mechanisms of methylation.

摘要

急性髓细胞白血病(AML)是一种异质性克隆性肿瘤,其特征是复杂的基因组改变。AML 的发病率随年龄增长而增加,大多数病例病情严重,预后不良。本研究基于基因表达数据库(GEO),探讨异常 DNA 甲基化与 AML 发生发展的关系,提取 AML 中与甲基化相关的数据,并鉴定出一个在 AML 患者原代细胞和正常骨髓造血干/祖细胞之间表达和分布差异显著的甲基化 CpG 位点。为了进一步研究甲基化位点功能障碍引起的差异,采用生物信息学分析筛选甲基化相关生物标志物,并通过单因素和多因素 Cox 比例风险回归选择潜在的预后基因。最后,确定了五个独立的预后指标。此外,这些结果为甲基化的分子机制提供了新的见解。

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