Biomarkers of peripheral blood neutrophil extracellular traps in the diagnosis and progression of malignant tumors

Abstract

Background and AimsThe mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor‐associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies.MethodsWe included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell‐free DNA (cfDNA), and systemic inflammation‐related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy.ResultsThe levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short‐term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation‐related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation‐related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors.ConclusionsChanges in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor‐induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy.

Neutrophil extracellular traps in cancer

“…Moreover, recent studies have reported that serum levels of H3Cit, as well as circulating MPO–DNA or NE–DNA complexes, are associated with the diagnosis and/or progression of multiple cancers with much more specificity. 51 , 78 , 136 , 148 , 167 , 179 , 180 , 184 , 188 , 191 , 194 These markers differentiate NETs from other types of nontumor‐derived cfDNA, which increases the likelihood of therapeutic translation. MPO–DNA or H3Cit has been employed in clinical trials as NETs biomarkers and prognostic indicators to evaluate the risk of thrombosis in patients with cancer including myeloproliferative neoplasms, pancreatic, gastric, 182 and colorectal cancer.…”