{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:47:18Z","timestamp":1785822438276,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate adenocarcinoma (PRAD) is a leading reason of cancer-related death in men worldwide, yet reliable biomarkers for accurate risk stratification are lacking. This study sought to build and test a lysosomal ferroptosis-related prognostic risk model for PRAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study merged single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets. Differentially expressed genes (DEGs) from the TCGA-PRAD cohort were intersected with 39 lysosomal ferroptosis-related genes (LFRGs). Univariate Cox regression and random survival forest (RSF) algorithms were applied to build a prognostic risk model, which was validated in two separate cohorts (GSE70768; GSE70769). Immune infiltration, drug sensitivity, and single-cell transcriptomic analyses were subsequently performed. Finally, the expression and potential mechanism of hub genes were investigated in experimental samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven candidate genes were identified, from which MMD and FTH1 were chosen to create a prognostic risk model. The model achieved AUC values of 0.90, 0.89, and 0.87 at 1-, 2-, and 3-year timepoints in TCGA-PRAD, with consistent performance across both validation cohorts. High-risk patients displayed an immunosuppressive microenvironment noted for enhanced myeloid-derived suppressor cells, regulatory T cells, upregulation of 23 immune checkpoint genes, higher TIDE scores, and increased tumor mutational burden (TMB). Drug sensitivity analysis identified differential responses to 3 agents after FDR correction. Single-cell analysis revealed myeloid-predominant expression of MMD and FTH1, with divergent pseudotime kinetics and enhanced KRAS, IL2-STAT5, and mTORC1 signaling, with MIF\u2013CD74 as a key intercellular communication axis. The hub genes were validated in experimental samples and these findings suggest a potential therapeutic strategy combining FTH1 degradation with PD-L1 blockade, although the immunological mechanisms require further validation in immunocompetent models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study presented a novel and potentially useful lysosomal ferroptosis-related prognostic risk model that effectively stratified PRAD patients by survival outcome and therapeutic response, providing a valuable framework for personalized clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1861663","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:37:47Z","timestamp":1785821867000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["New insights into lysosomal ferroptosis-related prognostic signatures in prostate cancer: evidence from bulk and single-cell transcriptomic analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Xudong","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oncology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beijing Hospital of Traditional Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Affiliated Traditional Chinese Medicine Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6417","DOI":"10.1039\/D5OB00603A","article-title":"Design, synthesis and evaluation of antiproliferative effects of ferritin-targeted degraders","volume":"23","author":"Ai","year":"2025","journal-title":"Org. 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