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Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence

BACKGROUND: Emerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents...

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Autores principales: Yan, Bin, Dai, Xuan, Ma, Quanfu, Wu, Xufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386589/
https://www.ncbi.nlm.nih.gov/pubmed/34458135
http://dx.doi.org/10.3389/fonc.2021.659445
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author Yan, Bin
Dai, Xuan
Ma, Quanfu
Wu, Xufeng
author_facet Yan, Bin
Dai, Xuan
Ma, Quanfu
Wu, Xufeng
author_sort Yan, Bin
collection PubMed
description BACKGROUND: Emerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents of several malignant tumors and affect the tumor microenvironment and cancer evolution. Here, we investigate the prognostic value of PMNs and NETs for recurrence in patients with cervical cancer. METHODS: The study comprised 126 cervical cancer patients who were retrospectively enrolled. CD66b(+) neutrophils and myeloperoxidase/citrullinated histone H3 (MPO/H3Cit)-labeled NETs were assessed by immunofluorescence, and the relationships with clinical and histopathologic features and patient outcome were evaluated. RESULTS: The highest density of CD66b(+) neutrophils were observed in the stromal compartment (median 55 cells/mm(2)). Above median densities of stromal CD66b(+) neutrophils and NETs were significantly associated with short recurrence-free survival (RFS) (P = 0.041 and P = 0.006, respectively). Multivariate analysis identified high clinical stage (hazard ratio [HR] 6.40; 95% confidence interval [CI] 3.51-11.64; P < 0.001), lymph node metastases (HR 4.69; 95% CI 3.09-9.66; P = 0.006) and high density of NETs (HR 2.66; 95% CI 1.21-5.82; P = 0.015) as independent prognostic factors for short RFS, whereas a high density of CD66b(+) neutrophils was not significant. Patients with a high NET density showed worse recurrence status in every stage, but the difference was only significant for stage I (P = 0.042), not stages II, III, or IV (all P > 0.05). Combining stromal NET density and the tumor, nodes, metastasis (TNM) staging system had better prognostic accuracy for cervical cancer than the TNM staging system alone at five and six years respectively (P = 0.010 and P = 0.023). CONCLUSION: Stromal NET density is an independent prognostic factor for RFS in cervical cancer. Combining NETs with the TNM staging system may further improve prognostic stratification.
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spelling pubmed-83865892021-08-26 Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence Yan, Bin Dai, Xuan Ma, Quanfu Wu, Xufeng Front Oncol Oncology BACKGROUND: Emerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents of several malignant tumors and affect the tumor microenvironment and cancer evolution. Here, we investigate the prognostic value of PMNs and NETs for recurrence in patients with cervical cancer. METHODS: The study comprised 126 cervical cancer patients who were retrospectively enrolled. CD66b(+) neutrophils and myeloperoxidase/citrullinated histone H3 (MPO/H3Cit)-labeled NETs were assessed by immunofluorescence, and the relationships with clinical and histopathologic features and patient outcome were evaluated. RESULTS: The highest density of CD66b(+) neutrophils were observed in the stromal compartment (median 55 cells/mm(2)). Above median densities of stromal CD66b(+) neutrophils and NETs were significantly associated with short recurrence-free survival (RFS) (P = 0.041 and P = 0.006, respectively). Multivariate analysis identified high clinical stage (hazard ratio [HR] 6.40; 95% confidence interval [CI] 3.51-11.64; P < 0.001), lymph node metastases (HR 4.69; 95% CI 3.09-9.66; P = 0.006) and high density of NETs (HR 2.66; 95% CI 1.21-5.82; P = 0.015) as independent prognostic factors for short RFS, whereas a high density of CD66b(+) neutrophils was not significant. Patients with a high NET density showed worse recurrence status in every stage, but the difference was only significant for stage I (P = 0.042), not stages II, III, or IV (all P > 0.05). Combining stromal NET density and the tumor, nodes, metastasis (TNM) staging system had better prognostic accuracy for cervical cancer than the TNM staging system alone at five and six years respectively (P = 0.010 and P = 0.023). CONCLUSION: Stromal NET density is an independent prognostic factor for RFS in cervical cancer. Combining NETs with the TNM staging system may further improve prognostic stratification. Frontiers Media S.A. 2021-08-11 /pmc/articles/PMC8386589/ /pubmed/34458135 http://dx.doi.org/10.3389/fonc.2021.659445 Text en Copyright © 2021 Yan, Dai, Ma and Wu https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Oncology
Yan, Bin
Dai, Xuan
Ma, Quanfu
Wu, Xufeng
Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title_full Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title_fullStr Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title_full_unstemmed Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title_short Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence
title_sort stromal neutrophil extracellular trap density is an independent prognostic factor for cervical cancer recurrence
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386589/
https://www.ncbi.nlm.nih.gov/pubmed/34458135
http://dx.doi.org/10.3389/fonc.2021.659445
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