Single‐Cell and Multiomic Analysis Reveals Neutrophil Heterogeneity and Prognostic Value in Cervical Lesions

ABSTRACT Cervical cancer is a prevalent malignancy among women, yet the involvement of neutrophils in its tumor microenvironment remains insufficiently explored. This study utilized single‐cell RNA sequencing (scRNA‐seq) to delineate neutrophil subsets and elucidate their roles in disease progression and prognosis. Analysis of 20 cervical biopsy samples across different disease stages identified five neutrophil subsets (N0–N4), among which the N4 subset exhibited a marked increase during disease advancement. Spatial transcriptomics and tissue microarray analyses revealed that N4 neutrophils are enriched in tumor regions and are associated with genes implicated in proliferation, metastasis, and immune evasion. Functional characterization demonstrated that N4 promotes tumor progression via activation of the Wnt signaling pathway and extracellular matrix remodeling. A neutrophil infiltration‐based risk model was established and validated through multi‐omics approaches, highlighting its potential in prognostic prediction. These findings underscore the pivotal role of N4 neutrophils in cervical cancer and provide valuable insights for the development of targeted immunotherapies and personalized treatment strategies.