Evidence map›Paper›PMID 35449078›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

Circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer.

Livia Ronchetti, Irene Terrenato, Margherita Ferretti, Giacomo Corrado, Frauke Goeman, Sara Donzelli, Chiara Mandoj, Roberta Merola, Ashanti Zampa, Mariantonia Carosi and 7 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 48 citations in OpenAlex.

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  3. Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 2 countries.

Livia Ronchetti *SAFU Unit, IRCCS - Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy.
Irene Terrenato *Clinical Trial Center - Biostatistics & Bioinformatics, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Margherita FerrettiSAFU Unit, IRCCS - Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy.
Giacomo CorradoDepartment of Women and Children Health, Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS - Università Cattolica del Sacro Cuore, Roma, Italy.
Frauke GoemanSAFU Unit, IRCCS - Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy.
Sara DonzelliOncogenomics and Epigenetics Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Chiara MandojClinical Pathology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Roberta MerolaClinical Pathology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Ashanti ZampaGynecologic Oncology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Mariantonia CarosiAnatomy Pathology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Giovanni BlandinoOncogenomics and Epigenetics Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Laura ContiClinical Pathology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Anna Maria LobascioGynecologic Oncology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Marcello IacobelliGynecologic Oncology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Enrico Vizza *Gynecologic Oncology Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
Giulia Piaggio *SAFU Unit, IRCCS - Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy.
Aymone Gurtner *SAFU Unit, IRCCS - Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy. aymone.gurtner@ifo.it.ORCID http://orcid.org/0000-0002-7661-9059
Istituti di Ricovero e Cura a Carattere Scientifico · ITIstituto di Farmacologia Traslazionale · ITUniversità Cattolica del Sacro Cuore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC).

methodsThe experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades.

resultsWe demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen.

conclusionOur data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.

Indexed as

Cell-Free Nucleic AcidsEndometrial NeoplasmsExtracellular TrapsBiomarkersFemaleHistonesHumansNeutrophilsBiomarkersCell-Free Nucleic AcidsHistonesCirculating cell-free DNACitrullinated Histone H3DNA cfDNA fragmentation patternDNA size distributionLiquid biopsyNETosisNETsNeutrophil ElastaseTumor induced systemic effects

Identifiers

PMID35449078
PMCPMC9027343
OpenAlexW4225787789

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.