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Int J Biol Sci 2023; 19(12):3951-3969. doi:10.7150/ijbs.85209 This issue Cite

Research Paper

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

Chengpeng Gui1,2,*✉, Jinhuan Wei1,*, Chengqiang Mo1,*, Yanping Liang3,*, Junjie Cen1, Yuhang Chen1, Daohu Wang1, Junhang Luo1,4✉

1. Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
3. Department of Laboratory Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
4. Institute of Precision Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
*Contributed equally

✉ Corresponding authors: Chengpeng Gui, Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China. Chengpeng.guica. Professor Luo Junhang, Department of Urology, First Affiliated Hospital, S More

Citation:
Gui C, Wei J, Mo C, Liang Y, Cen J, Chen Y, Wang D, Luo J. Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape. Int J Biol Sci 2023; 19(12):3951-3969. doi:10.7150/ijbs.85209. https://www.ijbs.com/v19p3951.htm
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Abstract

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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.

Keywords: tumor ageing microenvironment, antiandrogen therapy, immunotherapy, spatial transcriptomics, prostate cancer

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APA
Gui, C., Wei, J., Mo, C., Liang, Y., Cen, J., Chen, Y., Wang, D., Luo, J. (2023). Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape. International Journal of Biological Sciences, 19(12), 3951-3969. https://doi.org/10.7150/ijbs.85209.

ACS
Gui, C.; Wei, J.; Mo, C.; Liang, Y.; Cen, J.; Chen, Y.; Wang, D.; Luo, J. Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape. Int. J. Biol. Sci. 2023, 19 (12), 3951-3969. DOI: 10.7150/ijbs.85209.

NLM
Gui C, Wei J, Mo C, Liang Y, Cen J, Chen Y, Wang D, Luo J. Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape. Int J Biol Sci 2023; 19(12):3951-3969. doi:10.7150/ijbs.85209. https://www.ijbs.com/v19p3951.htm

CSE
Gui C, Wei J, Mo C, Liang Y, Cen J, Chen Y, Wang D, Luo J. 2023. Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape. Int J Biol Sci. 19(12):3951-3969.

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