Identification of Metastasis Driver Genesin HR-/HER۲+ Breast Cancer Using Data Mining Method

Background: Breast cancer (BC) is the most popular malignancyamong women. Despite all the advances, metastasis isthe leading cause of mortality among breast cancer patients.This study aims to find the dominant genes involved in thisevent among patients with HER۲-positive, ER/PGR-negativebreast cancer.Materials and Methods: This study integrated four microarrayprofile datasets obtained from GEO (Gene ExpressionOmnibus) database to illustrate potential leading candidategenes in HER۲+ breast cancer metastasis. Expression profilesGSE۳۲۶۴۶, GSE۵۸۹۸۴, GSE۷۶۲۷۴, and GSE۱۴۰۴۹۴, including۷۲ HER۲-Positive HR-Negative BC cases, were downloaded,sensitively integrated to share the same extractionmethod(Illumina) and platform (GPL۵۷۰), and deeply analyzedusing R software packages.Results: A total of ۳۲ shared differential expressed genes(DEGs) were identified. Twenty-seven genes were upregulated(logFC ≥ ۱.۵۰), and five were downregulated (logFC ≤ ۱.۵۰).The statistical significance was set to ۰.۰۵ for more accuracy(p ≤ ۰.۰۵).Conclusion: The downregulated genes show an inverse relationshipwith the overexpression of the HER۲ protein. Therefore,we suggest stopping the downregulation process mightlead to the blockage of distant metastasis in HER۲-positive ER/PGR-negative BC patients. Future pathway analysis is necessaryto secure the tumor suppressor effect of these genes.