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Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients
Beyond their critical role in hemostasis, platelets physically interact with neutrophils to form neutrophil‐platelet aggregates (NPAs), enhancing neutrophil effector functions during inflammation. NPAs may also promote disease worsening in various inflammatory diseases. However, characterization of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311065/ https://www.ncbi.nlm.nih.gov/pubmed/35253899 http://dx.doi.org/10.1002/ijc.33991 |
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author | Lecot, Pacôme Ardin, Maude Dussurgey, Sébastien Alcazer, Vincent Moudombi, Lyvia Pereira Abrantes, Manuela Hubert, Margaux Swalduz, Aurélie Hernandez‐Vargas, Hector Viari, Alain Caux, Christophe Michallet, Marie‐Cécile |
author_facet | Lecot, Pacôme Ardin, Maude Dussurgey, Sébastien Alcazer, Vincent Moudombi, Lyvia Pereira Abrantes, Manuela Hubert, Margaux Swalduz, Aurélie Hernandez‐Vargas, Hector Viari, Alain Caux, Christophe Michallet, Marie‐Cécile |
author_sort | Lecot, Pacôme |
collection | PubMed |
description | Beyond their critical role in hemostasis, platelets physically interact with neutrophils to form neutrophil‐platelet aggregates (NPAs), enhancing neutrophil effector functions during inflammation. NPAs may also promote disease worsening in various inflammatory diseases. However, characterization of NPAs in cancer remains totally unexplored. Using ImageStreamX (ISX) imaging flow cytometer, we were not only allowed able to detect CD15(+) CD14(−) CD36(+) ITGA2B(+) NPAs in both healthy donors' (HDs) and cancer patients' bloods, but we also showed that NPAs result from the binding of platelets preferentially to low‐density neutrophils (LDNs) as opposed to normal‐density neutrophils (NDNs). By reanalyzing two independent public scRNAseq data of whole blood leukocytes from cancer patients and HDs, we could identify a subset of neutrophils with high platelet gene expression that may correspond to NPAs. Moreover, we showed that cancer patients' derived NPAs possessed a distinct molecular signature compared to the other neutrophil subsets, independently of platelet genes. Gene ontology (GO) term enrichment analysis of this NPAs‐associated neutrophil transcriptomic signature revealed a significant enrichment of neutrophil degranulation, chemotaxis and trans‐endothelial migration GO terms. Lastly, using The Cancer Genome Atlas (TCGA), we could show by multivariate Cox analysis that the NPAs‐associated neutrophil transcriptomic signature was associated with a worse patient prognosis in several cancer types. These results suggest that neutrophils from NPAs are systemically primed by platelets empowering them with cancer progression capacities once at tumor site. NPAs may therefore hold clinical utility as novel noninvasive blood prognostic biomarker in cancer patients with solid tumors. |
format | Online Article Text |
id | pubmed-9311065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93110652022-07-29 Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients Lecot, Pacôme Ardin, Maude Dussurgey, Sébastien Alcazer, Vincent Moudombi, Lyvia Pereira Abrantes, Manuela Hubert, Margaux Swalduz, Aurélie Hernandez‐Vargas, Hector Viari, Alain Caux, Christophe Michallet, Marie‐Cécile Int J Cancer Tumor Markers and Signatures Beyond their critical role in hemostasis, platelets physically interact with neutrophils to form neutrophil‐platelet aggregates (NPAs), enhancing neutrophil effector functions during inflammation. NPAs may also promote disease worsening in various inflammatory diseases. However, characterization of NPAs in cancer remains totally unexplored. Using ImageStreamX (ISX) imaging flow cytometer, we were not only allowed able to detect CD15(+) CD14(−) CD36(+) ITGA2B(+) NPAs in both healthy donors' (HDs) and cancer patients' bloods, but we also showed that NPAs result from the binding of platelets preferentially to low‐density neutrophils (LDNs) as opposed to normal‐density neutrophils (NDNs). By reanalyzing two independent public scRNAseq data of whole blood leukocytes from cancer patients and HDs, we could identify a subset of neutrophils with high platelet gene expression that may correspond to NPAs. Moreover, we showed that cancer patients' derived NPAs possessed a distinct molecular signature compared to the other neutrophil subsets, independently of platelet genes. Gene ontology (GO) term enrichment analysis of this NPAs‐associated neutrophil transcriptomic signature revealed a significant enrichment of neutrophil degranulation, chemotaxis and trans‐endothelial migration GO terms. Lastly, using The Cancer Genome Atlas (TCGA), we could show by multivariate Cox analysis that the NPAs‐associated neutrophil transcriptomic signature was associated with a worse patient prognosis in several cancer types. These results suggest that neutrophils from NPAs are systemically primed by platelets empowering them with cancer progression capacities once at tumor site. NPAs may therefore hold clinical utility as novel noninvasive blood prognostic biomarker in cancer patients with solid tumors. John Wiley & Sons, Inc. 2022-03-18 2022-07-01 /pmc/articles/PMC9311065/ /pubmed/35253899 http://dx.doi.org/10.1002/ijc.33991 Text en © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Tumor Markers and Signatures Lecot, Pacôme Ardin, Maude Dussurgey, Sébastien Alcazer, Vincent Moudombi, Lyvia Pereira Abrantes, Manuela Hubert, Margaux Swalduz, Aurélie Hernandez‐Vargas, Hector Viari, Alain Caux, Christophe Michallet, Marie‐Cécile Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title | Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title_full | Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title_fullStr | Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title_full_unstemmed | Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title_short | Gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
title_sort | gene signature of circulating platelet‐bound neutrophils is associated with poor prognosis in cancer patients |
topic | Tumor Markers and Signatures |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311065/ https://www.ncbi.nlm.nih.gov/pubmed/35253899 http://dx.doi.org/10.1002/ijc.33991 |
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