Comprehensive multi-omics analysis identifies molecular subtypes and AMH-dependent mechanisms driving DTX resistance in prostate cancer.
- 1Department of Urology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, China.
- 2Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.
- 3Department of Colorectal and Anorectal Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou Central Hospital, Zhuzhou, China.
Abstract
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. 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. 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. 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.
Related
- Molecular Mechanisms of Quizartinib Resistance in FLT3 Mutants
- Mitoxyperilysis-based molecular subtyping identifies SPP1+ macrophages and IL1B as critical mediators of tumor progression and immunotherapy resistance in intrahepatic cholangiocarcinoma
- Transcriptomic analysis identifies candidate molecular mechanisms underlying SCF+G-CSF-reduced neuropathology in aged APP/PS1 mice.
- Novel strategies against drug-resistant tuberculosis: a comprehensive review from molecular mechanisms to clinical translation
- Molecular mechanisms and therapeutic strategies of immunotherapy resistance in esophageal cancer
BibTeX
@article{huang2026comprehensive,
title = {{Comprehensive multi-omics analysis identifies molecular subtypes and AMH-dependent mechanisms driving DTX resistance in prostate cancer.}},
author = {Liang Huang and Shusuan Jiang and Gongqian Zeng and Jun Gao and Hong Shan and Ke Huang},
journal = {Translational andrology and urology},
year = {2026},
month = sep,
doi = {10.21037/tau-2026-0290},
url = {https://europepmc.org/article/MED/42999584},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Comprehensive multi-omics analysis identifies molecular subtypes and AMH-dependent mechanisms driving DTX resistance in prostate cancer.
AU - Liang Huang
AU - Shusuan Jiang
AU - Gongqian Zeng
AU - Jun Gao
AU - Hong Shan
AU - Ke Huang
PY - 2026
DA - 2026/09/28
JO - Translational andrology and urology
DO - 10.21037/tau-2026-0290
UR - https://europepmc.org/article/MED/42999584
AB - 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. 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. 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. 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.
SN - 2223-4691
ER -