Bioinformatics-Based Prediction of Recurrence in Tamoxifen-Treated Patients with Estrogen Receptor-Positive Breast Cancer

Estrogen receptor (ER)-positive breast cancer is the most common subtype of all invasive breast cancer types.After binding with the ligand, the activated ER can promote cell proliferation while inhibiting cell apoptosis.Tamoxifen (TAM) acts as a selective ER modulator in adjuvant therapy for ER-positive breast cancer,inhibiting the proliferation of cancer cells and activating apoptosis. Although TAM treatment can drasticallydecrease mortality rates among breast cancer patients, about half of the patients still suffer from therecurrence of therapy resistance tumors. Therefore, identification of a molecular signature that predicts therelapse of TAM-treated patients could help the therapeutical management of ER-positive breast cancer.Here, we used network analysis to compare the responses of ER-positive breast cancer patients to TAM, assome patients developed metastasis while others showed partial or complete remission after treatment. To dothis, two microarray-based gene expression profiling datasets, GSE۹۸۹۳ and GSE۸۲۱۷۲ were downloadedfrom GEO. After merging the datasets and batch effect removal, differentially expressed genes (DEGs) wereobtained by comparing the expression values between recurrent and nonrecurrent breast cancer samples.Limma package was used to calculate fold changes of the DEGs. Next, we selected the genes with adjustedp-value <۰.۰۵ and Log۲ fold change <-۱ and >۱. Functional and pathway enrichment analyses of DEGs wereperformed using the Enrichr web server. Following network analysis within Cytoscape software, the hubgenes were identified by selecting the top ۱۰% of nodes harboring the highest degree of connectivity, usingthe cytoHubba plugin. In conclusion, we found that FN۱, ACTB, COL۱A۲, COL۳A۱, VIM, CTGF,YWHAZ, ACTA۲, LUM, and COL۴A۱ act as hub genes in the TAM-responsive regulatory network. Theresults can be helpful in predicting the response of ER-positive breast cancer patients to TAM and identifyingpatients who do not benefit from Tamoxifen treatment.

Keywords:

Breast cancer , ER-positive , Microarray , Recurrence , Tamoxifen