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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Signaling

Single-cell and Multi-omics Analyses Identify CAMP-Associated Neutrophil Remodeling during Radiochemotherapy in Cervical Cancer

  • Chongqing Health Center for Women and Children, Chongqing, China

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Abstract

Background: To investigate key genes and immune microenvironment dynamics in cervical cancer progression and radiochemotherapy (RCT), focusing on cathelicidin antimicrobial peptide (CAMP)-mediated neutrophil regulation. Methods: Integrated transcriptomic data from TCGA, GTEx, and GEO were analyzed to identify differentially expressed genes associated with cervical cancer (CC) and RCT. Prognostic genes were selected via univariate and multivariate Cox regression. Single-cell RNA sequencing (scRNA-seq) characterized cellular composition, gene expression, and neutrophil subsets. CAMP-high and CAMP-low neutrophils were analyzed for differential expression, functional enrichment, pseudotime trajectories, and cell–cell communication. Results: Three prognostic genes (CAMP, CCDC116, and GLB1L3) were identified, with CAMP highly expressed in cervical cancer tissues but markedly downregulated after RCT. At the single-cell level, CAMP showed significant differential expression in tumor-associated and RCT-related neutrophils. Differential analysis and GO enrichment of neutrophils stratified by CAMP expression revealed enhanced innate immune activation, cytokine signaling, and granule secretion features following RCT. Pseudotime analysis demonstrated that CAMP expression gradually increased as neutrophils differentiated toward tumor-associated states, whereas it significantly decreased at terminal states after RCT. Cell–cell communication analysis further indicated that CAMP-high neutrophils exhibited strengthened signaling with fibroblasts and epithelial cells, particularly involving key ligands such as CXCL, COL1, and LAMC; RCT effectively suppressed tumor-specific inflammatory and extracellular matrix remodeling signals. In vitro experiments show that CAMP promotes malignant proliferation and activates inflammatory pathways in cervical cancer, whereas RCT suppresses these effects and modulates the COL1A1/COL1A2–CD44 and ANXA1– 2 FPR1/FPR2 axes, reshaping tumor microenvironmental adhesion and immune activity. Conclusion: CAMP is a key regulator of neutrophil differentiation and tumor immune microenvironment remodeling in cervical cancer and during RCT. Its modulation of cell–cell communication networks suggest potential as a biomarker for treatment response and a therapeutic target.

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Keywords

cAMP, cervical cancer, Neutrophils, radiochemotherapy, single-cell sequencing

Received

22 December 2025

Accepted

13 February 2026

Copyright

© 2026 Li, Ran and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jing Li

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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