- Two molecular subtypes, C1 and C2, defined by DTX resistance gene signatures; C1 shows aggressive phenotype, shorter progression-free survival, immunosuppressive pathways.
- Single-cell analysis reveals AMH-low epithelial subpopulations are highly proliferative, carry greater mutational burden, and exhibit VEGF dominated intercellular signalling and DTX resistance.
- Subtype specific drug sensitivity estimates and immune pathway differences suggest candidate biomarkers and therapeutic targets, requiring further experimental and clinical validation.
Transl Androl Urol. 2026 Oct 30;15(10):371. doi: 10.21037/tau-2026-0290. Epub 2026 Sep 28.
ABSTRACT
BACKGROUND: Prostate cancer (PCa) remains one of the most prevalent malignancies and a leading cause of cancer-related mortality among men worldwide. Despite advancements in treatment, therapeutic resistance, particularly to docetaxel (DTX), significantly limits clinical efficacy and worsens patient outcomes.
METHODS: Transcriptomic profiles and matched clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were integrated for analysis. Differentially expressed genes linked to DTX resistance were screened to classify PCa patients into molecular subtypes. Bulk transcriptome-based drug sensitivity estimation and immune pathway enrichment analysis were performed to compare subtype-specific features. Single-cell transcriptomic data were further applied to resolve epithelial cell heterogeneity and interrogate the biological function of AMH in DTX-resistant epithelial subpopulations.
RESULTS: Two discrete molecular subtypes (C1 and C2) were established based on DTX resistance-related gene signatures. The C1 subtype displayed an aggressive phenotype with shorter progression-free survival (PFS), unique mutational landscapes, and activated immunosuppressive pathways. Subtypes also showed divergent sensitivity to multiple anticancer agents. Single-cell results demonstrated that AMH-high epithelial cells had low proliferation activity, limited genomic instability and weak DTX resistance. In contrast, AMH-low epithelial subpopulations were highly proliferative, carried a heavier mutational burden, and exhibited hyperactive intercellular communication dominated by VEGF signaling.
CONCLUSIONS: Collectively, these findings highlight the cellular and molecular heterogeneity associated with DTX resistance in PCa and provide new insights into the molecular characteristics of DTX resistance. These results may facilitate the identification of candidate biomarkers and potential therapeutic targets, although further experimental and clinical validation is required.
PMID:42999584 | PMC:PMC13743362 | DOI:10.21037/tau-2026-0290
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