Differential Expression and Pathway Analysis in Drug-Resistant Triple-Negative Breast Cancer Cell Lines Using RNASeq Analysis

Abstract

Triple-negative breast cancer (TNBC) is among the most notorious types of breast cancer, the treatment of which does not give consistent results due to the absence of the three receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as well as high amount of molecular variability. Drug resistance also contributes to treatment unresponsiveness. We studied differentially expressed genes, their biological roles, as well as pathways from RNA-Seq datasets of two different TNBC drug-resistant cell lines of Basal B subtype SUM159 and MDA-MB-231 treated with drugs JQ1 and Dexamethasone, respectively, to elucidate the mechanism of drug resistance. RNA sequencing(RNA-Seq) data analysis was done using edgeR which is an efficient program for determining the most significant Differentially Expressed Genes (DEGs), Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. iPathway analysis was further used to obtain validated results using analysis that takes into consideration type, function, and interactions of genes in the pathway. The significant similarities and differences throw light into the molecular heterogeneity of TNBC, giving clues into the aspects that can be focused to overcome drug resistance. From this study, cytokine-cytokine receptor interaction pathway appeared to be a key factor in TNBC drug resistance.

GDF10 inhibits proliferation and epithelial-mesenchymal transition in triple‐negative breast cancer via upregulation of Smad7

“…The resulting datasets offer possibilities for researching its molecular bases and testing new therapeutic strategies from multiple angles [8]. This is aided by the burgeoning field of bioinformatics, which allows to analyze biological data derived from high-throughput methods [9]. Among those, RNA-Seq is a highly efficient method for transcriptome sequencing and detection of gene expression [10].…”

High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery

“…They found that the cytokine-cytokine receptor interaction pathway in these two cell lines showed consistent significantly differentially expressed. It provided new ideas for the development of new drugs to treat TNBC (Shaheen et al, 2018).…”

The role of photodynamic therapy on multidrug resistant breast cancer

“…This tumor type will likely respond and receive endocrine therapy, while HER2+ breast cancers will receive HER2 targeted therapies. A negative expression of these biomarkers is called triple-negative breast cancer (TNBC) which comprises 15–20% of all breast cancers [21, 22]. TNBC is the most serious type of tumor and its molecular classification is characterized by a negative profile of ER, PR, and HER2 [23].…”

“…TNBC is the most serious type of tumor and its molecular classification is characterized by a negative profile of ER, PR, and HER2 [23]. According to Shaheen et al [22], these receptors helps in targeted therapy and effective treatment of breast tumors. Histopathologic features of this tumor include a high nuclear mitotic activity with a high nuclear-cytoplasmic ratio that accelerate its proliferation and make its’ metastases highly difficult to recognize, hence referred to as metastases with unknown origin [23].…”