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拷贝数变异在腔面B型乳腺肿瘤基因共表达模式中的作用

The Role of Copy Number Variants in Gene Co-Expression Patterns for Luminal B Breast Tumors.

作者信息

Hernández-Gómez Candelario, Hernández-Lemus Enrique, Espinal-Enríquez Jesús

机构信息

Computational Genomics Division, National Institute of Genomic Medicine, Mexico City, Mexico.

Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, Mexico.

出版信息

Front Genet. 2022 Apr 1;13:806607. doi: 10.3389/fgene.2022.806607. eCollection 2022.

Abstract

Gene co-expression networks have become a usual approach to integrate the vast amounts of information coming from gene expression studies in cancer cohorts. The reprogramming of the gene regulatory control and the molecular pathways depending on such control are central to the characterization of the disease, aiming to unveil the consequences for cancer prognosis and therapeutics. There is, however, a multitude of factors which have been associated with anomalous control of gene expression in cancer. In the particular case of co-expression patterns, we have previously documented a phenomenon of loss of long distance co-expression in several cancer types, including breast cancer. Of the many potential factors that may contribute to this phenomenology, copy number variants (CNVs) have been often discussed. However, no systematic assessment of the role that CNVs may play in shaping gene co-expression patterns in breast cancer has been performed to date. For this reason we have decided to develop such analysis. In this study, we focus on using probabilistic modeling techniques to evaluate to what extent CNVs affect the phenomenon of long/short range co-expression in Luminal B breast tumors. We analyzed the co-expression patterns in chromosome 8, since it is known to be affected by amplifications/deletions during cancer development. We found that the CNVs pattern in chromosome 8 of Luminal B network does not alter the co-expression patterns significantly, which means that the co-expression program in this cancer phenotype is not determined by CNV structure. Additionally, we found that region 8q24.3 is highly dense in interactions, as well as region p21.3. The most connected genes in this network belong to those cytobands and are associated with several manifestations of cancer in different tissues. Interestingly, among the most connected genes, we found MAF1 and POLR3D, which may constitute an axis of regulation of gene transcription, in particular for non-coding RNA species. We believe that by advancing on our knowledge of the molecular mechanisms behind gene regulation in cancer, we will be better equipped, not only to understand tumor biology, but also to broaden the scope of diagnostic, prognostic and therapeutic interventions to ultimately benefit oncologic patients.

摘要

基因共表达网络已成为整合来自癌症队列基因表达研究的大量信息的常用方法。基因调控控制的重编程以及依赖于这种控制的分子途径是疾病特征的核心,旨在揭示对癌症预后和治疗的影响。然而,有许多因素与癌症中基因表达的异常控制有关。在共表达模式的特定情况下,我们之前已经记录了几种癌症类型(包括乳腺癌)中远距离共表达丧失的现象。在可能导致这种现象的众多潜在因素中,拷贝数变异(CNV)经常被讨论。然而,迄今为止,尚未对CNV在塑造乳腺癌基因共表达模式中可能发挥的作用进行系统评估。因此,我们决定开展此类分析。在本研究中,我们专注于使用概率建模技术来评估CNV在多大程度上影响Luminal B型乳腺肿瘤中的长/短程共表达现象。我们分析了8号染色体上的共表达模式,因为已知它在癌症发展过程中会受到扩增/缺失的影响。我们发现Luminal B型网络8号染色体上的CNV模式并未显著改变共表达模式,这意味着这种癌症表型中的共表达程序不是由CNV结构决定的。此外,我们发现8q24.3区域和p21.3区域的相互作用高度密集。该网络中连接最多的基因属于那些细胞带,并且与不同组织中癌症的几种表现相关。有趣的是,在连接最多的基因中,我们发现了MAF1和POLR3D,它们可能构成基因转录的调控轴,特别是对于非编码RNA物种。我们相信,通过深入了解癌症中基因调控背后的分子机制,我们不仅将更好地理解肿瘤生物学,而且还将扩大诊断、预后和治疗干预的范围,最终使肿瘤患者受益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d33/9010943/c976db6db06e/fgene-13-806607-g001.jpg

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