Identification of Mitochondrial-Related Genes as Potential Biomarkers for Docetaxel-Resistant Prostate Cancer
Abstract
Objectives: Prostate cancer (PC) is the most common cancer among men worldwide and a significant cause of cancer-related deaths. Docetaxel (DX), a taxane-based chemotherapeutic agent, was the first treatment to exhibit substantial efficacy in the management of PC. This study aims to demonstrate the mitochondrial genes that are affected by DX in PC using bioinformatics analysis.
Materials and Methods: For bioinformatics analysis, mRNA microarray data from DX-sensitive PC cell lines (DU145) and DX-resistant cell lines (DU145-DR), corresponding to the study GSE36135, were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed and identified using the Transcriptome Analysis Console 4.0 (TAC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to pinpoint significant genes and biological pathways associated with DX therapy. Additionally, proteinprotein interaction network analysis was conducted to identify critical proteins and interactions within these pathways.
Results: TAC applied criteria of an adjusted p-value <0.05, (false discovery rate-FDR<0.05) and |log2FC| >1.0 to identify DEGs. The analysis revealed the upregulation of 515 genes and the downregulation of 608 genes in DX-treated cells compared to controls. Enrichment analysis of DEGs indicated their involvement in pathways such as metabolic pathways, pathways of neurodegeneration involving multiple diseases, biosynthesis of cofactors, chemical carcinogenesis mediated by reactive oxygen species, valine, leucine, and isoleucine degradation, carbon metabolism, and oxidative phosphorylation. Among these, ALDH4A1, ALDH6A1, ALDH2, PCCB, GLS, GATM, GLS2, IDH2, SUCLG2, ECI2, GLDC, IVD, ALDH7A1, ACACA, ALDH5A1, NDUFS7, PCK2, ARG2, FDXR, and CPT1A were identified as the most significant candidate genes.
Conclusion: This comprehensive bioinformatics analysis sheds light on the molecular mechanisms underlying DX’s action and highlights potential targets for combination therapies, offering promising strategies to enhance treatment efficacy in PC.
Ethical Statement
Not applicable. This paper does not involve human or animal subjects
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Details
| Primary Language | English |
|---|---|
| Subjects | Craniofacial Biology |
| Journal Section | Articles |
| Authors | |
| Publication Date | July 1, 2025 |
| Submission Date | January 22, 2025 |
| Acceptance Date | April 9, 2025 |
| Published in Issue | Year 2025 Volume: 79 Issue: 2 |