Neutrophil extracellular traps as biomarkers for predicting prognosis and chemotherapy response in colorectal cancer.

[UNLABELLED] Colorectal cancer (CRC) is a prevalent malignancy with high mortality. Neutrophil extracellular traps (NETs) are implicated in metastasis and chemotherapy resistance, making them potential biomarkers for prognosis and treatment response. We extracted NETs-related genes (NRGs) from neutrophil transcriptome data derived from in vitro-treated cells and used LASSO regression to construct a NETs risk score model. Then we validated it in multiple public CRC datasets. Serum citrullinated histone H3 (CitH3) levels were measured in 146 CRC patients and 49 healthy controls by enzyme-linked immunosorbent assay (ELISA) to evaluate diagnostic and prognostic utility, as well as chemotherapy response prediction. The model demonstrated robust prognostic performance (AUC = 0.745-0.762 for 1-5 year survival), with high-risk patients exhibiting significantly reduced survival ( < 0.0001) and compromised treatment efficacy. CitH3 levels were markedly elevated in CRC patients, particularly in those with poor prognosis and chemotherapy resistance, suggesting diagnostic and predictive utility. This study establishes NETs-based risk scoring as an effective tool for CRC prognosis and treatment response prediction, while serum CitH3 emerges as a promising biomarker for diagnosis and monitoring.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1038/s41598-025-29093-0.