The identification of highly upregulated genes in claudin-low breast cancer through an integrative bioinformatics approach

Hatem Zayed

doi:10.1016/j.compbiomed.2020.103806

Abstract

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). The upregulated genes were the focus of this study, 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, using MetaCore, Cortellis solution software, 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 sheds light on the molecular pathology of CLBC and might provide a potential biomarkers for the treatment of CLBC.

Highlights

Cancer is a broad set of diseases wherein cells divide, grow, and invade other parts of the body abnormally and without control
A comprehensive bioinformatics approach was performed to identify the pathways and genes that were significantly enriched between the SUM159 claudin-low breast cancer (CLBC) cell line expressing microRNA-203 and control cells
The microarray data were obtained from the GEO database with ID GSE50697

Summary

Introduction

Cancer is a broad set of diseases wherein cells divide, grow, and invade other parts of the body abnormally and without control. Among all the different types of cancers identified to date, breast cancer (BC) accounts for 14% of cancers in women and is the second most commonly occurring cancer worldwide (Ferlay et al 2013; Thirumal Kumar and George Priya Doss 2016b, 2017). The majority of patients present with symptoms of BC, which includes a lump in the breast, a distortion in breast shape, dimpling of the skin of the breast, fluid impending from the nipple, a newly inverted nipple or a red or scaly patch of skin of the breast, approximately 40% cases are diagnosed by the NHS breast screening program when they are asymptomatic (Sibbering and Courtney 2016) This UK-based screening method, according to the evidence provided by Threlfall et al reduces BC mortality (Threlfall, Collins, and Woodman 2003)

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