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Parishani M, Fazilati M, Nazem H, Salavati H, Mahdevar M. Comprehensive Analysis of ATP Synthase-binding Cassette Transporter Genes in Breast Cancer: Prognostic Value of ABCD1, ABCA5. Res Mol Med (RMM) 2024; 12 (4)
URL: http://rmm.mazums.ac.ir/article-1-581-fa.html

Background: ATP synthase-binding cassette (ABC) membrane transporter genes play a crucial role in mediating drug resistance and may serve as predictive biomarkers for treatment outcomes in breast cancer (BC). This study aimed to examine changes in the expression of these genes.
Methods: Transcriptome data from BC were extracted from the Cancer Genome Atlas (TCGA), normalized, and categorized into malignant and healthy samples. Immunohistochemistry data examined protein levels, and linear models were used to evaluate variations in gene expression. Kaplan-Meier curves and Cox regression analysis were used to investigate the correlations with survival. Data from PharmacoDB were utilized to examine the relationship between drug sensitivity and resistance. RNA extraction and cDNA synthesis were performed on samples from the Iranian Tumor Bank, and quantitative reverse transcription
polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCA5 and ABCD1.

Results: Differential expression analysis identified eight ABC transporter genes with upregulated expression and 19 genes with downregulated expression in BC tissues compared to healthy samples. Specifically, high ABCD1 expression was correlated with poor prognosis, whereas higher levels of ABCA10, ABCA5, ABCA8, ABCB1, and ABCD2 were associated with improved patient outcomes. Protein expression analysis corroborated these findings. Co-expression network and pathway enrichment analyses revealed that ABCD1 is involved in glycolysis, oxidative phosphorylation, and DNA repair pathways. The other candidate genes were linked to ABC transporter activity and fatty acid metabolism. Furthermore, ROC curve analysis demonstrated high sensitivity and specificity of the candidate genes in distinguishing malignant from normal tissues. Resistance to Docetaxel was linked to elevated expression of ABCA5, ABCA8, ABCA10, and ABCB1, which needs more confirmation. Our ex vivo studies revealed a notable difference in ABCA5 and ABCD1 levels between cancerous samples and healthy tissues.
Conclusion: This study highlights the potential of ABC transporter genes, particularly ABCD1, ABCA10, ABCA5, ABCA8, ABCB1, and ABCD2, as novel prognostic biomarkers and contributors to drug resistance in BC. Their involvement in key oncogenic pathways underscores their significance in BC pathophysiology and warrants further investigation for therapeutic targeting.