ArticleFrontiers in immunology2025
Succinylation-related molecular activities in cancer: metabolic adaptations, immune landscape, and prognostic significance in colorectal cancer.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Artificial-intelligence- and multi-omics-guided predictive and drug repurposing framework construction for colorectal cancer: evidence from succinylation-neutrophil signatures.Frontiers in cell and developmental biology · 2026Article
- Sensing succinate: SUCNR1 as a context-dependent metabolic and cellular signal integrator.Frontiers in molecular biosciences · 2026Review
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- DAPK1-positve macrophages facilitate immunosuppressive microenvironment and determine immunotherapy efficacy in colorectal cancer.Journal of translational medicine · 2025Article
- Identification of prognostic biomarkers and development of a prediction model for prostate cancer.Frontiers in immunology · 2025Article
- Succinate in innate immunity: linking metabolic reprogramming to immune modulation.Frontiers in immunology · 2025Review
- Succinylation heterogeneity in lung adenocarcinoma: from prognostic model to KLK6-driven tumor microenvironment remodeling.Frontiers in immunology · 2025Article
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4 authors.
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Abstract
Background: Succinylation, a key post-translational modification, plays a crucial role in metabolic regulation and tumor progression. However, its influence on the tumor immune microenvironment and its prognostic implications remain unclear. A systematic pan-cancer analysis of succinylation-related molecular activities is needed. Methods: Bulk transcriptomic, single-cell RNA sequencing, and spatial transcriptomic data across pan-cancer from TCGA, GEO, TISCH, and multiple other databases were analyzed. Succinylation scores were calculated using Gene Set Variation Analysis (GSVA). The interactions between succinylation scores, immune infiltration, tumor microenvironment, tumor mutational burden, and immunotherapy response were assessed. A succinylation-based prognostic model was constructed and validated in colorectal cancer (CRC) cohorts. PCED1A protein expression was evaluated by immunohistochemistry and Western blotting. The function of PCED1A in CRC was investigated through Results: Succinylation scores were significantly altered in multiple tumor types. Higher succinylation scores correlated with mitochondrial oxidative phosphorylation, while lower succinylation scores were linked to immune cell differentiation. Spatial transcriptomic analysis showed a negative correlation between succinylation scores and immune cell activity in tumor-adjacent regions. A prognostic model consisting of 11 succinylation-related genes (ATP6V1C2, CAPS, DAPK1, P4HA1, PCED1A, RASL10B, AGT, EREG, HYAL1, SARAF, and SLC4A4) was developed. High-risk patients exhibited significantly shorter overall survival. PCED1A was upregulated in CRC and positively associated with SIRT5. Overexpression of PCED1A promoted intracellular protein desuccinylation, along with enhanced CRC cell proliferation, migration, and invasion. Conclusion: Our analysis demonstrates that succinylation-related molecular activities display distinct expression patterns across cancers, which are associated with metabolic regulation, immune modulation, and disease prognosis. The succinylation-based prognostic model provides a novel risk stratification tool for CRC, while PCED1A-dependent succinylation regulation may serve as a potential therapeutic target.
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