Predicting biomarker microRNAs for differentiating ER/PR positive and negative breast cancers using bioinformatics

Backgrounds: Breast cancer (BC) is the most common malignancy in females and despitesignificant advancements in treatment strategies; it remains the second leading cause of cancerrelateddeath worldwide. Classification of BC is based on hormone-receptors expression statusand identifying the molecular subtypes of BC plays a crucial role in the treatment approach andmonitoring the efficacy of therapy. The majority of BCs have shown overexpression of estrogenreceptors (ERs) and progesterone receptors (PRs). Furthermore, evaluation of ER and PR inbreast tumors is important for prognosis and management of therapy. According to recentstudies, dysregulation of small none-coding RNAs such as miRNAs is involved in the initiationand progression of a variety of diseases including BC. Therefore, miRNAs can be considered asnon-invasive biomarkers for diagnose of the ER/PR-positive and -negative breast tumors.Materials and Methods: We investigated the differentially expressed miRNAs in differentsubtypes of breast tumors by reanalyzing the available data in TCGA, GSE۲۶۴۵۹, GSE۲۰۶۸۵and GSE۲۹۱۷۳. In the next step, other databases including UCSC, SRA, mirBase and RNAfoldwere used to clarify some characteristics of our candidate miRNAs such as conservation,expression status within tumor and non-tumor tissues, and their secondary structure, respectively.Moreover, some bioinformatics online tools such as miRDB, MiRnalyze, KEGG, andTargetScanHuman ۷.۱ were applied to predict potential target genes for our candidate miRNAs.Results: This study indicates that due to the specificity (AUC = ۰.۹۳۸) of our candidatemiRNAsin differentiating ER/PR positive and negative breast tumors, they could represent a newbiomarker for Luminal and none-Luminal breast cancer diagnosis.Conclusion: We identified ten candidate miRNAs with significant differential expression withinER/PR-positive and -negative breast tumors. Some of these miRNAs play pivotal roles inregulating the expression of ER/PR hormone receptors. These miRNAs will allow us toincorporate such method for identifying patients who are most likely responding to specifictherapies based on ER/PR status.

کلیدواژه ها:

Breast cancer ، Estrogen receptors ، Progesterone receptors ، miRNAs ، Biomarker