Integrative single-cell and spatial multi-Omics analyses identify NETs-driven colon cancer subtypes with distinct...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Colon cancer is a leading cause of cancer deaths with high recurrence rates.
• The tumor microenvironment (TME) significantly impacts tumor progression and treatment resistance.
• Neutrophil extracellular traps (NETs) are implicated in tumor invasion, metastasis, and immune evasion, but their role in colon cancer is unclear.

Purpose of the Study:

• To investigate the role of NETs-associated genes in colon cancer.
• To identify molecular subtypes and develop a prognostic model for colon cancer based on NETs-related genes.

Main Methods:

• Transcriptomic analyses using TCGA and GEO datasets.
• Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics.
• Multivariate Cox and LASSO regression for prognostic model construction and validation.
• Colocalization analysis of genetic data.

Main Results:

• Two distinct NETs-related molecular subtypes of colon cancer were identified with differences in immune composition and metabolism.
• NETs-high colon cancer cells exhibit metabolic reprogramming linked to immune escape and therapeutic resistance.
• A four-gene prognostic signature (ARRDC1, TUBB2A, DUSP5, SLC2A3) demonstrated moderate prognostic discrimination.
• Increased TUBB2A expression correlated with adverse clinical outcomes.

Conclusions:

• NETs-associated genes are critical in colon cancer progression, immune modulation, and metabolic reprogramming.
• The identified four-gene signature is a potential candidate biomarker for colon cancer risk stratification, requiring further validation.