Neutrophil extracellular trap-associated risk index for predicting outcomes and response to Wnt signaling inhibitors...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Triple-negative breast cancer (TNBC) presents a poor prognosis due to metastasis and therapy resistance.
• Neutrophil extracellular traps (NETs) are implicated in breast cancer progression and serve as a TNBC biomarker.

Purpose of the Study:

• To identify NET-related genes and develop a predictive risk index for TNBC.
• To investigate the association between NETs, TNBC progression, and therapeutic response, particularly to Wnt signaling pathway inhibitors.

Main Methods:

• Utilized bulk and single-cell RNA sequencing data from public databases.
• Identified five NET-related genes and constructed NET-related subgroups.
• Developed a risk index based on differentially expressed genes between subgroups and conducted in vitro verification experiments.

Main Results:

• Established a risk index comprising three pivotal genes, differentiating high-risk and low-risk TNBC patient groups.
• High-risk group exhibited worse prognosis, advanced clinicopathological features, and poorer therapy response.
• Low-risk group showed enrichment in the Wnt signaling pathway, predicting higher sensitivity to Wnt inhibitors; in vitro studies confirmed reduced tumor cell migration, invasion, proliferation, and enhanced drug sensitivity in low-risk cells.

Conclusions:

• Multi-omics analysis reveals NET-associated genes influence TNBC occurrence, progression, and treatment.
• The developed risk index effectively predicts TNBC patient populations likely to benefit from Wnt signaling pathway inhibitor therapy.