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The identification of highly upregulated genes in claudin-low breast cancer through an integrative bioinformatics approach.
Computers in Biology and Medicine ( IF 7.0 ) Pub Date : 2020-05-30 , DOI: 10.1016/j.compbiomed.2020.103806
Hatem Zayed 1
Affiliation  

Breast cancer (BC) is one of the leading causes of cancer-related death among women worldwide, and claudin-low breast cancer (CLBC) is a subtype of BC that remains poorly described. This study aimed to identify upregulated genes and significant pathways involved in CLBC. The SUM159 cell line is derived from human CLBC tissue; the GSE50697 dataset contains three replicates of SUM159 cells treated with pBabe puro miR-203 and three replicates of control SUM159 cells (pBabe puro). The data were normalized and upregulated, and downregulated genes were identified based on the logFC values. Gene Ontology (GO) and pathway analysis identified the most significant pathways and genes involved in CLBC pathogenesis. A total of 156 significant genes were identified (69 upregulated genes and 64 downregulated genes). From the pathway analysis, the senescence-associated secretory phenotype, which involves the CXCL8, IL1A, and IL6 genes, was found to be mapped through more than one pathway (WikiPathways and Reactome). From the refined GO analysis, the IL-13 signaling pathway was identified; this pathway includes the IL6, CXCL8, VEGF-C, NRG1, and EREG genes, which were mapped as hub genes in several pathogenesis pathways. From the survival analysis, high levels of IL6, CXCL8, and EREG were related to high survival rates, and low levels of VEGFC and NRG1 were related to high survival rates. The IL6 and CXCL8 genes were the most significant and the most highly represented in the GO and refined GO analyses. This study might provide a potential biomarker for the treatment of CLBC.



中文翻译:

通过整合的生物信息学方法鉴定克劳丁蛋白低的乳腺癌中高度上调的基因。

乳腺癌(BC)是全世界女性与癌症相关的死亡的主要原因之一,而克劳丁低乳腺癌(CLBC)是BC的一种亚型,至今仍缺乏描述。这项研究旨在确定CLBC中涉及的上调基因和重要途径。SUM159细胞系衍生自人CLBC组织。GSE50697数据集包含经pBabe puro miR-203处理的SUM159细胞的三个重复和对照SUM159细胞(pBabe puro)的三个重复。数据被标准化和上调,并且基于logFC值鉴定出下调的基因。基因本体论(GO)和途径分析确定了CLBC发病机理中最重要的途径和基因。总共鉴定出156个重要基因(69个上调基因和64个下调基因)。从路径分析来看发现CXCL8IL1AIL6基因通过多种途径(WikiPathways和Reactome)进行定位。从精炼的GO分析中,可以确定IL-13信号通路。该途径包括IL6,CXCL8,VEGF-C,NRG1EREG基因,它们在几种发病途径中被定位为中枢基因。从生存分析来看,高水平的IL6,CXCL8EREG与高生存率有关,而低水平的VEGFCNRG1与高生存率有关。该IL6CXCL8这些基因在GO和精细的GO分析中是最重要和最有代表性的。该研究可能为CLBC的治疗提供潜在的生物标志物。

更新日期:2020-05-30
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