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Updated: Aug 21, 2026
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
New insights into lysosomal ferroptosis-related prognostic signatures in prostate cancer: evidence from bulk and
Xudong Zhu1, Xixi Ji2, Hao Liu1
1Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Background:
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.
Methods:
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.
Results:
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-CD74 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.
Conclusion:
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.
