METTL1-driven nucleotide metabolism reprograms the immune microenvironment in hepatocellular carcinoma: a multi-omics approach for prognostic biomarker discovery DOI Creative Commons

Xie Weng,

Yangyue Huang,

Zhen Fu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 22, 2025

Background Hepatocellular carcinoma (HCC) remains one of the leading causes cancer-related mortality worldwide, partly due to an incomplete understanding metabolic and immune dysregulation driving its progression. Here, we uncover a novel role METTL1 in nucleotide metabolism reprogramming, which significantly modulates tumor microenvironment. Methods Utilizing integrated multi-omics approach, analyzed metabolism-related genes derived from TCGA, GEO, ICGC datasets. Non-negative matrix factorization (NMF) clustering stratified HCC patients into distinct subgroups with varied clinical features. Weighted Gene Co-expression Network Analysis (WGCNA) identified hub that were subsequently used construct robust prognostic models via multiple machine learning algorithms. These computational findings validated through vitro experiments, infiltration assessments, single-cell RNA sequencing analysis. Results Our analyses demonstrate is markedly upregulated HCC, reprogramming expression key checkpoints, including PD-L1 CTLA-4. This regulation associated immunosuppressive microenvironment, reduced activated T cells, poorer outcomes. Moreover, model integrating checkpoint profiles shows strong predictive performance across independent cohorts, highlighting potential utility. Conclusion study highlights innovative METTL1-driven reshaping microenvironment HCC. The provide insights pathogenesis pave way for developing personalized therapeutic strategies based on targeting pathways.

Language: Английский

METTL1-driven nucleotide metabolism reprograms the immune microenvironment in hepatocellular carcinoma: a multi-omics approach for prognostic biomarker discovery DOI Creative Commons

Xie Weng,

Yangyue Huang,

Zhen Fu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 22, 2025

Background Hepatocellular carcinoma (HCC) remains one of the leading causes cancer-related mortality worldwide, partly due to an incomplete understanding metabolic and immune dysregulation driving its progression. Here, we uncover a novel role METTL1 in nucleotide metabolism reprogramming, which significantly modulates tumor microenvironment. Methods Utilizing integrated multi-omics approach, analyzed metabolism-related genes derived from TCGA, GEO, ICGC datasets. Non-negative matrix factorization (NMF) clustering stratified HCC patients into distinct subgroups with varied clinical features. Weighted Gene Co-expression Network Analysis (WGCNA) identified hub that were subsequently used construct robust prognostic models via multiple machine learning algorithms. These computational findings validated through vitro experiments, infiltration assessments, single-cell RNA sequencing analysis. Results Our analyses demonstrate is markedly upregulated HCC, reprogramming expression key checkpoints, including PD-L1 CTLA-4. This regulation associated immunosuppressive microenvironment, reduced activated T cells, poorer outcomes. Moreover, model integrating checkpoint profiles shows strong predictive performance across independent cohorts, highlighting potential utility. Conclusion study highlights innovative METTL1-driven reshaping microenvironment HCC. The provide insights pathogenesis pave way for developing personalized therapeutic strategies based on targeting pathways.

Language: Английский

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