Elevation of circulating neutrophil extracellular traps in endometrial cancer: Poor prognostic value of cell-free double-stranded DNA

Yeonju Seo; Se Ik Kim; Sang Hoon Song; Jisoo G. Kim; Ja-Yoon Gu; Hye Won Jeon; Maria Lee; Hyun Kyung Kim

Translational Oncology (Nov 2024)

Elevation of circulating neutrophil extracellular traps in endometrial cancer: Poor prognostic value of cell-free double-stranded DNA

Yeonju Seo,
Se Ik Kim,
Sang Hoon Song,
Jisoo G. Kim,
Ja-Yoon Gu,
Hye Won Jeon,
Maria Lee,
Hyun Kyung Kim

Affiliations

Yeonju Seo: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
Se Ik Kim: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
Sang Hoon Song: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea
Jisoo G. Kim: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
Ja-Yoon Gu: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Hye Won Jeon: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea; Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea
Maria Lee: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea; Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea; Corresponding author at: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Hyun Kyung Kim: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Corresponding author at: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.

Journal volume & issue: Vol. 49
p. 102072

Abstract

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Objective: Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer. Methods: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer. Results: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760–0.889), histone-DNA complex (0.740; 95 % CI, 0.660–0.809), and neutrophil elastase (0.689; 95 % CI, 0.607–0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659–0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer. Conclusion: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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