Integrative Bioinformatic analysis of differentially expressed genes and miRNA regulation in neoadjuvant chemotherapy resistance in HER۲+ breast cancer

Breast cancer is the most common type of cancer and the second leading cause of cancerrelateddeaths among women globally [۱]. Patients who are initially diagnosed with locally advancedbreast cancer are typically advised to undergo neoadjuvant chemotherapy (NAC) as a standard treatmentapproach. The effectiveness of therapy for breast cancer can vary among different populations. Hence,drug resistance is a significant factor contributing to the failure of cancer therapy [۲], [۳]. MiRNAs playa crucial role in negatively regulating genes by binding to the ۳' untranslated region (۳'UTR) of mRNAsand have been identified as significant contributors to drug resistance [۴]. The main aim of this study isto identify Differentially Expressed Genes (DEGs) in patients sensitive and resistant to NAC to discoverpotential biomarkers related to drug resistance. We perform bulk RNA sequencing on the GSE۱۶۲۱۸۷dataset to find hub genes. RNA sequencing was performed using the Galaxy server, and DEG wasobtained with DESeq۲. As a result, ۶۳ DEG with p.value < ۰.۰۵ and adjusted p-value < ۰.۰۵ was found.Significant lncRNAs are up-regulated in resistant patients, such as LINC۰۱۲۹۱, LINC۰۱۲۸۵, andLINC۰۱۸۱۹. A candidate gene, GSTM۱, had a significantly low expression in resistant patients (LogFC= -۱۰.۸۳). This gene belongs to the glutathione S-transferase family, which could provide resistanceto several anticancer drugs by collaborating with efflux transporters and multidrug resistance proteins[۵]. To discover miRNA that may have a role in down-regulating this gene in resistant patients, we usedTarBase-v۹.۰, and hsa-miR-۲۱۰-۳p was found, which is shown in many studies that this miRNAupregulation is involved in cancer development and therapeutic response [۶]. In conclusion, we foundessential genes involved in NAC resistance and suggest an axis of GSTM۱/hsa-miR-۲۱۰-۳p has a rolein this manner.

کلیدواژه ها:

Breast cancer ، Drug resistance ، RNA sequencing ، miRNAs