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转座元件在急性髓系白血病转录组和预后中的表达。

Transposable Element Expression in Acute Myeloid Leukemia Transcriptome and Prognosis.

机构信息

Jane Anne Nohl Division of Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern California, Los Angeles, California, 90033, USA.

Center for Epigenetics, Van Andel Research Institute, 333 Bostwick Ave NE, Grand Rapids, MI, 49503, USA.

出版信息

Sci Rep. 2018 Nov 6;8(1):16449. doi: 10.1038/s41598-018-34189-x.

DOI:10.1038/s41598-018-34189-x
PMID:30401833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6219593/
Abstract

Over half of the human genome is comprised of transposable elements (TE). Despite large-scale studies of the transcriptome in cancer, a comprehensive look at TE expression and its relationship to various mutations or prognosis has not been performed. We characterized the expression of TE in 178 adult acute myeloid leukemia (AML) patients using transcriptome data from The Cancer Genome Atlas. We characterized mutation specific dysregulation of TE expression using a multivariate linear model. We identified distinct patterns of TE expression associated with specific mutations and transcriptional networks. Genes regulating methylation was not associated with significant change in TE expression. Using an unpenalized cox regression analysis we identified a TE expression signature that predicted prognosis in AML. We identified 14 candidate prognostic TE transcripts (TEP) that classified AML as high/low-risk and this was independent of mutation-based and coding-gene expression based risk-stratification. TEP was able to predict prognosis in independent cohorts of 284 pediatric AML patients and 19 relapsed adult AML patients. This first comprehensive study of TE expression in AML demonstrates that TE expression can serve as a biomarker for prognosis in AML, and provides novel insights into the biology of AML. Studies characterizing its role in other cancers are warranted.

摘要

人类基因组的一半以上由转座元件 (TE) 组成。尽管对癌症的转录组进行了大规模研究，但尚未全面观察 TE 表达及其与各种突变或预后的关系。我们使用来自癌症基因组图谱的转录组数据，对 178 名成人急性髓系白血病 (AML) 患者的 TE 表达进行了特征描述。我们使用多元线性模型来描述 TE 表达的突变特异性失调。我们确定了与特定突变和转录网络相关的不同 TE 表达模式。调节甲基化的基因与 TE 表达的显著变化无关。使用无惩罚的 cox 回归分析，我们确定了一个 TE 表达特征，可预测 AML 的预后。我们鉴定了 14 个候选预后 TE 转录本 (TEP)，这些转录本将 AML 分为高/低风险，这与基于突变和编码基因表达的风险分层无关。TEP 能够预测 284 名儿科 AML 患者和 19 名复发的成人 AML 患者的独立队列的预后。这是 AML 中 TE 表达的首次全面研究，表明 TE 表达可以作为 AML 预后的生物标志物，并为 AML 的生物学提供了新的见解。有必要对其在其他癌症中的作用进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/365fbc2bc2a3/41598_2018_34189_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/2159e354c48c/41598_2018_34189_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/9086d35dedb7/41598_2018_34189_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/e9e7ed350b9f/41598_2018_34189_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/16b32b203682/41598_2018_34189_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/36bcf871e266/41598_2018_34189_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/416f7de6c437/41598_2018_34189_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/365fbc2bc2a3/41598_2018_34189_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/2159e354c48c/41598_2018_34189_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/9086d35dedb7/41598_2018_34189_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/e9e7ed350b9f/41598_2018_34189_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/16b32b203682/41598_2018_34189_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/36bcf871e266/41598_2018_34189_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/416f7de6c437/41598_2018_34189_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce6/6219593/365fbc2bc2a3/41598_2018_34189_Fig7_HTML.jpg

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