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Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape

Background: 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 microenvir...

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Autores principales: Gui, Chengpeng, Wei, Jinhuan, Mo, Chengqiang, Liang, Yanping, Cen, Junjie, Chen, Yuhang, Wang, Daohu, Luo, Junhang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411471/
https://www.ncbi.nlm.nih.gov/pubmed/37564213
http://dx.doi.org/10.7150/ijbs.85209
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author Gui, Chengpeng
Wei, Jinhuan
Mo, Chengqiang
Liang, Yanping
Cen, Junjie
Chen, Yuhang
Wang, Daohu
Luo, Junhang
author_facet Gui, Chengpeng
Wei, Jinhuan
Mo, Chengqiang
Liang, Yanping
Cen, Junjie
Chen, Yuhang
Wang, Daohu
Luo, Junhang
author_sort Gui, Chengpeng
collection PubMed
description Background: 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. Methods: 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. Results: 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, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: 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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spelling pubmed-104114712023-08-10 Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape Gui, Chengpeng Wei, Jinhuan Mo, Chengqiang Liang, Yanping Cen, Junjie Chen, Yuhang Wang, Daohu Luo, Junhang Int J Biol Sci Research Paper Background: 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. Methods: 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. Results: 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, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: 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. Ivyspring International Publisher 2023-07-31 /pmc/articles/PMC10411471/ /pubmed/37564213 http://dx.doi.org/10.7150/ijbs.85209 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Gui, Chengpeng
Wei, Jinhuan
Mo, Chengqiang
Liang, Yanping
Cen, Junjie
Chen, Yuhang
Wang, Daohu
Luo, Junhang
Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title_full Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title_fullStr Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title_full_unstemmed Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title_short Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
title_sort therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411471/
https://www.ncbi.nlm.nih.gov/pubmed/37564213
http://dx.doi.org/10.7150/ijbs.85209
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