Establishing AMACR as an AR-Derived Biomarker in Prostate Cancer: Metabolic and Androgen- Mediated Mechanisms


Authors : Madhab Mondal; Prerna Rai; Akash Baglari; Divyadarshi Rai; Pratiksha Chhetri; Purandar Sarkar

Volume/Issue : Volume 10 - 2025, Issue 9 - September


Google Scholar : https://tinyurl.com/yw8ncrjk

Scribd : https://tinyurl.com/565h88z5

DOI : https://doi.org/10.38124/ijisrt/25sep352

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Abstract : Prostate cancer (PCa) progression is primarily driven by androgen receptor (AR) signaling, which orchestrates tumor proliferation and metabolic reprogramming. Alpha-Methyl Acyl-CoA Racemase (AMACR) is a key enzyme in branched-chain fatty acid β-oxidation which is widely recognized as a diagnostic marker for PCa but its regulatory association with AR and functional implications remain unclear. Using globally available multi-omics datasets, we analyzed RNA-seq profiles from TCGA-PRAD which revealed significant overexpression of AMACR in tumors compared to normal tissues (p < 0.001). Elevated AMACR levels correlated with advanced Gleason scores, nodal positivity, and poor overall survival (p = 0.027). Functional insights from androgen stimulation and antagonism datasets, along with Chipset analyses, demonstrated direct AR occupancy at enhasssncer regions near AMACR which further confirms androgen-dependent transcriptional regulation. Protein-level evidence from immunohistochemistry and immunofluorescence supported these findings. Collectively, these results establish AMACR as an AR-regulated biomarker in PCa, implicating it in metabolic dysregulation and disease aggressiveness, and highlight its potential as a therapeutic target within the androgen-driven oncogenic network.

Keywords : Prostate cancer, AMACR, Androgen receptor, Biomarker.

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Prostate cancer (PCa) progression is primarily driven by androgen receptor (AR) signaling, which orchestrates tumor proliferation and metabolic reprogramming. Alpha-Methyl Acyl-CoA Racemase (AMACR) is a key enzyme in branched-chain fatty acid β-oxidation which is widely recognized as a diagnostic marker for PCa but its regulatory association with AR and functional implications remain unclear. Using globally available multi-omics datasets, we analyzed RNA-seq profiles from TCGA-PRAD which revealed significant overexpression of AMACR in tumors compared to normal tissues (p < 0.001). Elevated AMACR levels correlated with advanced Gleason scores, nodal positivity, and poor overall survival (p = 0.027). Functional insights from androgen stimulation and antagonism datasets, along with Chipset analyses, demonstrated direct AR occupancy at enhasssncer regions near AMACR which further confirms androgen-dependent transcriptional regulation. Protein-level evidence from immunohistochemistry and immunofluorescence supported these findings. Collectively, these results establish AMACR as an AR-regulated biomarker in PCa, implicating it in metabolic dysregulation and disease aggressiveness, and highlight its potential as a therapeutic target within the androgen-driven oncogenic network.

Keywords : Prostate cancer, AMACR, Androgen receptor, Biomarker.

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Paper Submission Last Date
31 - December - 2025

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