Evaluation the expression level of ATP1A2, FXYD1 and ADCY3 in tumor and marginal tissues of patients with breast cancer

Abstract

Breast cancer (BC) is One of the most common malignancies in women and a leading cause of mortality for them globally. Multiple molecular mechanisms are involved in the pathogenesis of this heterogeneous disease. Understanding these additional pathways might help develop new breast cancer treatment strategies, so targeting different signaling pathways and other deregulated genes directly or indirectly could be effective for targeting breast cancer in the future. The main aim of the present study is to identify the gene expression signature of breast cancer to unveil disease etiology mechanisms. After bioinformatics investigation and determination of cAMP signaling pathway as the deregulated cascade, this study aimed to evaluate expression level of ATP1A2, FXYD1and ADCY3 in tumoral and non-tumoral adjacent tissues of patients with breast cancer among the differentially expressed genes (DEGs).

Methods: Microarray data sets named GSE70947 and GSE70905 of breast tumoral and non-tumoral adjacent tissues form the Gene Expression Omnibus (GEO) database were downloaded. The limma package in the R software was used to identify DEGs in single data set analysis, also the two data sets underwent gene-expression meta-analysis using INMEX data base. After determining the list of DEGs and according to enrichment study using EnrichR library, ATP1A2, FXYD1 and ADCY3, members of cAMP signaling pathway, were subjected to Real-time PCR quantification to examine their expression level. Hence, real-time PCR conducted on fifty BC tumoral and non-tumoral adjacent tissues to evaluate the expression level of the three mRNAs. Results: According to the meta-analysis with INMEX, DEGs with statistically significance expression level (Adjusted P-value <0.05 and |LogFC| >=0.5) included 656 up regulated and 543 down regulated genes. Enrichment analysis using the DEGs revealed the cAMP signaling pathways as the most enriched term. In this molecular pathway, ATP1A2, FXYD1 were among top 10 downregulated genes and ADCY3 was an important member of the cascade. Although the expression levels of these genes in clinical samples showed an upregulation in BC tumoral versus non-tumoral adjacent tissues.