Academic Journal
Integrative methylation and transcriptomic analysis reveals key genes linking cellular senescence and metabolic reprogramming in colorectal liver metastasis.
| Τίτλος: | Integrative methylation and transcriptomic analysis reveals key genes linking cellular senescence and metabolic reprogramming in colorectal liver metastasis. |
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| Συγγραφείς: | Ma X; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China., Chen L; Department of Hepatobiliary Cancer, Liver cancer research center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China., Yi C; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China., Li Y; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China., Geng Y; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China., Tao B; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China., Chen J; Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China. |
| Πηγή: | Bioscience trends [Biosci Trends] 2026 Jan 07; Vol. 19 (6), pp. 672-683. Date of Electronic Publication: 2025 Oct 31. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: International Research and Cooperation Association for Bio & Socio-Sciences Advancement Country of Publication: Japan NLM ID: 101502754 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1881-7823 (Electronic) Linking ISSN: 18817815 NLM ISO Abbreviation: Biosci Trends Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Tokyo : International Research and Cooperation Association for Bio & Socio-Sciences Advancement |
| Ιατρικοί όροι (MeSH): | Liver Neoplasms*/secondary , Liver Neoplasms*/genetics , Liver Neoplasms*/metabolism , Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/metabolism , DNA Methylation*/genetics , Cellular Senescence*/genetics , Cellular Reprogramming*/genetics, Chemokine CXCL1/genetics ; Plasminogen Activator Inhibitor 1/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Biomarkers, Tumor/genetics ; Oxaliplatin/pharmacology ; Oxaliplatin/therapeutic use ; Humans ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Transcriptome ; Epigenesis, Genetic ; Metabolic Reprogramming ; Cell Cycle Proteins ; N-myc Downstream-Regulated Gene 1 Protein |
| Περίληψη: | Colorectal liver metastasis (CRLM) remains lethal, and the convergence of cellular senescence with metabolic reprogramming via epigenomic rewiring is poorly understood. We integrated genome-wide DNA methylation and RNA-seq data from 10 paired primary tumors and liver metastases (GSE213402). After calling differentially methylated genes (3,399 hyper- and 9,519 hypomethylated) and differentially expressed genes (406 DEGs), we intersected them with curated senescence (n = 866) and metabolic reprogramming (n = 948) gene sets, yielding 28 differentially expressed cellular-senescence-related genes (DE-CSRGs) and 24 metabolic-reprogramming-related genes (DE-MRRGs). Machine-learning pipelines (LASSO + SVM-RFE) converged on a five-gene signature: CXCL1, SERPINE1, NDRG1, SRM and GATM, most of which are hypomethylated and over-expressed in metastases. Gene-set enrichment analysis revealed that these genes are involved in pathways such as oxidative phosphorylation, focal adhesion, complement-coagulation cascades, and PPAR signaling. Immune de-convolution revealed strong positive correlations between signature genes and immunosuppressive subsets (MDSCs, Tregs, type-1 T-helper cells; p < 0.05). Elevated IC |
| Contributed Indexing: | Keywords: DNA hypomethylation; chemoresistance; immunosuppressive microenvironment; machine-learning signature; polyamine metabolism |
| Substance Nomenclature: | 0 (Chemokine CXCL1) 0 (Plasminogen Activator Inhibitor 1) 0 (Intracellular Signaling Peptides and Proteins) U3P01618RT (Fluorouracil) 0 (Biomarkers, Tumor) 04ZR38536J (Oxaliplatin) 0 (Cell Cycle Proteins) EC 2.7.11.1 (N-myc Downstream-Regulated Gene 1 Protein) 0 (CXCL1 protein, human) 0 (SERPINE1 protein, human) |
| Entry Date(s): | Date Created: 20251103 Date Completed: 20260107 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.5582/bst.2025.01297 |
| PMID: | 41183917 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1881-7823 |
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| DOI: | 10.5582/bst.2025.01297 |