Multi-omics analysis reveals that neutrophil extracellular traps related gene TIMP1 promotes CRC progression and influences ferroptosis.

Abstract

Background: Previous studies have found that neutrophil extracellular traps (NETs) are highly expressed in colorectal cancer (CRC) and are associated with poor prognosis. Currently, there are few studies on the relationship between NETs and CRC, so we tried to explore new markers based on NETs to assist in the treatment of CRC.

Method: We jointly screened three major NETs genes through machine learning. Large-sample RNA transcriptome and single-cell transcriptome analysis further confirmed that TIMP1 is a core gene in NETs. We used small interfering RNA to knockdown TIMP1, and verified the ability of TIMP1 in CRC proliferation, invasion and migration through western blot, transwell, cell scratch assay, cell clone formation and other experiments.

Result: We screened out three major NETs Genes: TIMP1, F3, and CRISPLD2 based on machine learning. The NETs score constructed based on this not only predicts the prognosis of CRC patients but also shows significant differences in MSI status, chenckpoints expression, and predicted efficacy of PD-L1 targeted therapy. Transcriptome and single-cell data reveal that TIMP1 is highly expressed in neutrophils and is associated with poor prognosis in colorectal cancer patients and the occurrence of ferroptosis. Biological experiments have proven that TIMP1 can promote the proliferation, invasion and migration of CRC.

Conclude: Bioinformatics analysis combined with experimental verification showed that TIMP1 is related to ferroptosis and plays a promoting role in the invasion, migration and proliferation of CRC.