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This poses a challenge to the clinical relevance of pre-clinical models and the efficacy of contemporary therapeutic approaches. Here we develop the snFLARE-seq and mxFRIZNGRND methodologies to directly investigate the transcriptomic and metabolomic landscape of prostate cancer patients utilizing formalin-fixed paraffin-embedded (FFPE) specimens. A retrospective analysis reveals the clinical disparities of prostate cancer from peripheral zone (PZ), transition zone (TZ), and across PZ and TZ. The snFLARE-seq, refined for enhanced single-nucleus sequencing, unveils distinct cell type distributions and signaling pathways between PZ and TZ samples. Hormone therapy substantially affects cancer cells and microenvironment, leading to a polarized feature of epithelial cells and a subverted immune microenvironment. With improvements in metabolite extraction, mxFRIZNGRND reveals unique metabolic features of prostate cancer from different origins. The metabolomic results indicate that PZ cancer cells are in a metabolic-dormant status, which are probably awaken by hormone therapy. Integrative analysis of results from snFLARE-seq, mxFRIZNGRND, and TCGA database uncovers four metabolic pathways and related genes associated with disease aggressiveness. Our work could accelerate investigations on disease heterogeneity and evolution in real-world clinical settings, stimulating patient-specific precision healthcare solutions.<\/jats:p>","DOI":"10.1038\/s41467-026-69347-7","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T03:44:59Z","timestamp":1770435899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of the transcriptomic and metabolomic landscape of prostate cancer with different anatomical origins using snFLARE-seq and mxFRIZNGRND"],"prefix":"10.1038","volume":"17","author":[{"given":"Dongyin","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-5133","authenticated-orcid":false,"given":"Haoran","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6355-1992","authenticated-orcid":false,"given":"Kai","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbing","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-7200","authenticated-orcid":false,"given":"Shaozhuo","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinsheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyan","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-4453","authenticated-orcid":false,"given":"Shan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqin","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-3092","authenticated-orcid":false,"given":"Shengsong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-667X","authenticated-orcid":false,"given":"Hongqian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3960-0068","authenticated-orcid":false,"given":"Luonan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-2756","authenticated-orcid":false,"given":"Huiru","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-431X","authenticated-orcid":false,"given":"Zhenfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"69347_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. 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