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探讨 ETV6-RUNX1 阳性小儿 B 细胞急性淋巴细胞白血病中的 lncRNA-mRNA 共表达网络。

Investigation of lncRNA-mRNA co-expression network in ETV6-RUNX1-positive pediatric B-cell acute lymphoblastic leukemia.

机构信息

Department of Hematology Laboratory, Yantai Yuhuangding Hospital, Yantai, P.R. China.

出版信息

PLoS One. 2021 Jun 8;16(6):e0253012. doi: 10.1371/journal.pone.0253012. eCollection 2021.

DOI:10.1371/journal.pone.0253012
PMID:34101758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8186766/
Abstract

ETV6/RUNX1 gene fusion is the most common chromosomal translocation abnormality occurred in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Compared with ETV6-RUNX1-negative patients, ETV6-RUNX1-positive patients possess more improved treatment strategies but higher risk to relapse. In this research, the potential gene interaction networks were constructed intending for elucidating the pathogenesis of B-ALL. We performed the weighted gene co-expression network analysis (WGCNA) to assess the involvement of lncRNA-mRNA pairs in B-ALL patients consisting of 24 ETV6-RUNX1-positive patients and 18 ETV6-RUNX1-negative patients and found a module that was significantly associated with positive/negative trait. Gene Ontology analysis showed that mRNAs in this module were enriched in the positive regulation of MAPK cascade, positive regulation of JNK cascade, and myeloid cell differentiation pathway. To further investigate the relationship between lncRNAs and mRNAs in this significant module, we constructed the lncRNA-mRNA co-expression network. 3 lncRNAs (RP11-170J3.2, RP11-135F9.1 and RP1-151B14.9) were found at the core of the lncRNA-mRNA co-expression network, which had the most co-expression connections with mRNAs. And several related mRNAs (ACTN1, TNFRSF21 and NLRP3) had a significant correlation with the patient survival prediction. Our findings may explicate the pathogenesis of B-ALL, and the disease-associated genes could provide clues to find novel biomarkers for prognosis.

摘要

ETV6/RUNX1 基因融合是儿童 B 细胞急性淋巴细胞白血病(B-ALL)中最常见的染色体易位异常。与 ETV6-RUNX1 阴性患者相比,ETV6-RUNX1 阳性患者拥有更多改进的治疗策略,但复发风险更高。在这项研究中,我们构建了潜在的基因互作网络,旨在阐明 B-ALL 的发病机制。我们对包括 24 例 ETV6-RUNX1 阳性患者和 18 例 ETV6-RUNX1 阴性患者的 B-ALL 患者进行了加权基因共表达网络分析(WGCNA),发现了一个与阳性/阴性特征显著相关的模块。基因本体论分析表明,该模块中的 mRNAs 富集于 MAPK 级联的正调控、JNK 级联的正调控和髓样细胞分化途径。为了进一步研究该显著模块中 lncRNA 和 mRNAs 之间的关系,我们构建了 lncRNA-mRNA 共表达网络。在该共表达网络的核心位置发现了 3 个 lncRNA(RP11-170J3.2、RP11-135F9.1 和 RP1-151B14.9),它们与 mRNAs 的共表达连接最多。几个相关的 mRNAs(ACTN1、TNFRSF21 和 NLRP3)与患者的生存预测有显著相关性。我们的研究结果可能阐明了 B-ALL 的发病机制,疾病相关基因可能为寻找新的预后标志物提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/084a9d0fe6f5/pone.0253012.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/5225ab463195/pone.0253012.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/084a9d0fe6f5/pone.0253012.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/5225ab463195/pone.0253012.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/66a956b5690f/pone.0253012.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/4c2e427ab3c9/pone.0253012.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea3f/8186766/084a9d0fe6f5/pone.0253012.g006.jpg

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