解析乳腺癌分子亚型中与免疫相关的长链非编码RNA

Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes.

作者信息

Mathias Carolina, Muzzi João Carlos Degraf, Antunes Bruna Borba, Gradia Daniela F, Castro Mauro A A, Carvalho de Oliveira Jaqueline

机构信息

Department of Genetics, Federal University of Parana, Post-graduation Program in Genetics, Curitiba, Brazil.

Bioinformatics and Systems Biology Lab, Federal University of Parana (UFPR), Polytechnic Center, Curitiba, Brazil.

出版信息

Front Oncol. 2021 May 31;11:692170. doi: 10.3389/fonc.2021.692170. eCollection 2021.

Abstract

Breast cancer (BRCA) is the most leading cause of cancer worldwide. It is a heterogeneous disease with at least five molecular subtypes including luminal A, luminal B, basal-like, HER2-enriched, and normal-like. These five molecular subtypes are usually stratified according to their mRNA profile patterns; however, ncRNAs are increasingly being used for this purpose. Among the ncRNAs class, the long non-coding RNAs (lncRNAs) are molecules with more than 200 nucleotides with versatile regulatory roles; and high tissue-specific expression profiles. The heterogeneity of BRCA can also be reflected regarding tumor microenvironment immune cells composition, which can directly impact a patient's prognosis and therapy response. Using BRCA immunogenomics data from a previous study, we propose here a bioinformatics approach to include lncRNAs complexity in BRCA molecular and immune subtype. RNA-seq data from The Cancer Genome Atlas (TCGA) BRCA cohort was analyzed, and signal-to-noise ratio metrics were applied to create these subtype-specific signatures. Five immune-related signatures were generated with approximately ten specific lncRNAs, which were then functionally analyzed using GSEA enrichment and survival analysis. We highlighted here some lncRNAs in each subtype. LINC01871 is related to immune response activation and favorable overall survival in basal-like samples; EBLN3P is related to immune response suppression and progression in luminal B, MEG3, XXYLT1-AS2, and LINC02613 were related with immune response activation in luminal A, HER2-enriched and normal-like subtypes, respectively. In this way, we emphasize the need to know better the role of lncRNAs as regulators of immune response to provide new perspectives regarding diagnosis, prognosis and therapeutical targets in BRCA molecular subtypes.

摘要

乳腺癌(BRCA)是全球癌症的首要病因。它是一种异质性疾病,至少有五种分子亚型,包括腔面A型、腔面B型、基底样型、HER2富集型和正常样型。这五种分子亚型通常根据其mRNA谱模式进行分层;然而,非编码RNA(ncRNA)越来越多地用于此目的。在ncRNA类别中,长链非编码RNA(lncRNA)是具有200多个核苷酸的分子,具有多种调节作用;并且具有高度的组织特异性表达谱。BRCA的异质性也可以在肿瘤微环境免疫细胞组成方面得到体现,这可以直接影响患者的预后和治疗反应。利用先前一项研究中的BRCA免疫基因组学数据,我们在此提出一种生物信息学方法,将lncRNA的复杂性纳入BRCA分子和免疫亚型中。对来自癌症基因组图谱(TCGA)BRCA队列的RNA测序数据进行了分析,并应用信噪比指标来创建这些亚型特异性特征。用大约十种特定的lncRNA生成了五个免疫相关特征,然后使用基因集富集分析(GSEA)和生存分析对其进行功能分析。我们在此突出了每个亚型中的一些lncRNA。LINC01871与基底样样本中的免疫反应激活和良好的总生存期相关;EBLN3P与腔面B型中的免疫反应抑制和进展相关,MEG3、XXYLT1-AS2和LINC02613分别与腔面A型、HER2富集型和正常样型亚型中的免疫反应激活相关。通过这种方式,我们强调需要更好地了解lncRNA作为免疫反应调节因子的作用,以便为BRCA分子亚型的诊断、预后和治疗靶点提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18f/8202402/470df6271c54/fonc-11-692170-g001.jpg

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