The Impact of Olaparib on Metabolic Pathways in Triple Negative Breast Cancer: A Bioinformatics Approach

Öz

Aim: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer (BC) characterized by the lacking estrogen receptors, progesterone receptors, and HER2 expression, making it challenging to treat with targeted therapies. Olaparib, a PARP inhibitor, has shown promise in treating TNBC, particularly in patients with BRCA1 or BRCA2 mutations. This study aims to elucidate the metabolic pathways affected by olaparib in TNBC using bioinformatics analysis. Material and Method: For bioinformatics analysis, mRNA microarray data of control MDA-MB-468 cells (non-treated) and OlaR MDA-MB-468 (3μM olaparib-treated MDA-MB-468 cells) with the study numbered GSE165914 were downloaded from Gene Expression Omnibus (GEO) database. GEO2R was used to analyze and identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) analysis were carried out for DEGs to determine significant genes and the biological pathways influenced by olaparib treatment. Protein-protein interaction (PPI) network analysis further identified key proteins and interactions within these pathways. Results: For GEO2R analysis adjusted P-value<0.05 and |log2FC|>1.0 were selected. The results revealed the upregulation of 2277 genes and downregulation of 2298 genes in olaparib-treated cells compared to the controls. It was reported that DEGs enriched in pathways including, metabolic pathways, pathways in cancer, chemical carcinogenesis - reactive oxygen species, cell cycle, autophagy - animal, Efferocytosis and TNF signaling pathway. Both upregulated and downregulated DEGs were associated with metabolic pathways. Moreover, NDUFA5, NDUFA6, NDUFS6, NDUFB3, NDUFB10, NDUFB7, NDUFA7, NDUFA9, H2AC8, H2AC13, H2AC17, H4C11, H4C12, H2BC12, H2BC21 and H2BC4 were identified as the most significant candidate genes. Conclusion: This comprehensive bioinformatics approach provides insights into the molecular mechanisms of olaparib's action and identifies potential targets for combination therapies to enhance treatment efficacy in breast cancer.

Anahtar Kelimeler

• Triple-negative breast cancer
• olaparib
• bioinformatics
• gene expression omnibus
• gene expression

Destekleyen Kurum

N/A

Etik Beyan

N/A

Teşekkür

N/A

Kaynakça

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