ArticleJournal of translational medicine2026
Integrative single-cell and spatial multi-Omics analyses identify NETs-driven colon cancer subtypes with distinct metabolic features and prognostic implications.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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Who cites it
1 citing paper in PubMed.
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
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12 authors.
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Abstract
backgroundColon cancer remains one of the leading causes of cancer-related deaths worldwide and is associated with high rates of recurrence and metastasis despite advances in therapy. The tumor microenvironment (TME), characterized by complex immune and stromal interactions, plays a pivotal role in tumor progression and treatment resistance. Neutrophil extracellular traps (NETs), an emerging component of the TME, have been implicated in promoting tumor invasion, metastasis, and immune evasion. However, their specific role in colon cancer remains unclear.
methodsComprehensive transcriptomic analyses were conducted using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify NETs-associated genes involved in colon cancer. Single-cell RNA sequencing (scRNA-seq) was utilized to assess cellular heterogeneity, and spatial transcriptomics mapped NETs activity and cell-cell interactions within the TME. A prognostic model was constructed using multivariate Cox and LASSO regression analyses based on key NETs-related genes. Model performance was validated using internal and external cohorts. Additionally, colocalization analysis between TUBB2A eQTL signals and colorectal cancer overall survival GWAS effects was performed to investigate potential genetic correlations.
resultsTwo distinct NETs-related molecular subtypes of colon cancer were identified, differing in immune composition, metabolic activity, and gene expression profiles. NETs-high malignant cells demonstrated metabolic reprogramming involving oxidative phosphorylation and cellular respiration, contributing to immune escape and therapeutic resistance. A four-gene prognostic signature (ARRDC1, TUBB2A, DUSP5, and SLC2A3) was developed and showed moderate prognostic discrimination across internal and external cohorts, indicating potential value for risk stratification but limited predictive accuracy at the current stage. Colocalization analysis revealed a modest negative correlation between TUBB2A expression and overall survival and cancer-specific survival, suggesting that increased TUBB2A expression may be associated with adverse clinical outcomes.
conclusionsThis study reveals that NETs-associated genes play crucial roles in colon cancer progression, immune modulation, and metabolic reprogramming. The identified four-gene signature may serve as a candidate biomarker for risk stratification in colon cancer, although further validation is needed.
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