AI Article Synopsis
- Numerous studies link aging with the progression of prostate cancer (PCa), but this research is the first to explore the specific characteristics of the aging microenvironment (AME) in PCa and create an aging microenvironment index (AMI) that predicts patient outcomes and responses to immunotherapy.
- The study identified three distinct AME regulatory patterns in 813 PCa patients, revealing their connection to different clinical prognoses and physiological pathways; higher AMI scores were linked to more immune cell infiltration, increased biochemical recurrence, and poorer responses to treatments.
- Additionally, in lab experiments, combining bicalutamide and embelin effectively reduced PCa tumor growth, while the main
Article Abstract
Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, and act as oncogenes and were verified via in vivo and in vitro experiments. AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411471 | PMC |
| http://dx.doi.org/10.7150/ijbs.85209 | DOI Listing |
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