NETs biomarkers in saliva and serum OSCC patients: One hypothesis, two conclusions

OSCC 患者唾液和血清中的 NETs 生物标志物:一个假设,两个结论

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作者:Marzena Garley, Dorota Dziemiańczyk-Pakieła, Wioletta Ratajczak-Wrona, Anna Pryczynicz, Karolina Nowak, Bogdan Łazarczyk, Ewa Jabłońska

Conclusions

The results obtained from the saliva of cancer patients suggest an impairment of the immunological homeostasis within the oral cavity related to NET formation, the causes of which should be sought in deficient activation of NADPH oxidase.

Material and methods

Expression of myeloperoxidase (MPO), and histones H2A, H2B, H3 in the tumor tissue, was investigated using immunohistochemistry. The expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: p47-phox, p67-phox (neutrophil cytosolic factor 2, NCF2) and panRac, as well as citrullinated histone H3 (CitH3) in peripheral blood neutrophil lysates, was assessed via Western blot. ELISA tests were employed to measure the concentrations of circulating free DNA (cfDNA) and MPO in saliva only, and NOX1, NCF2, DNASE1 in saliva and serum.

Methods

Expression of myeloperoxidase (MPO), and histones H2A, H2B, H3 in the tumor tissue, was investigated using immunohistochemistry. The expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: p47-phox, p67-phox (neutrophil cytosolic factor 2, NCF2) and panRac, as well as citrullinated histone H3 (CitH3) in peripheral blood neutrophil lysates, was assessed via Western blot. ELISA tests were employed to measure the concentrations of circulating free DNA (cfDNA) and MPO in saliva only, and NOX1, NCF2, DNASE1 in saliva and serum.

Purpose

The actual role of neutrophils and neutrophil extracellular traps (NETs) in the course of cancer has not been clearly defined. The aim of this study was to determine the clinical usefulness of NETs biomarkers in saliva in confrontation with the blood serum and tumor tissue as a potential prognostic and therapeutic target in patients with oral squamous cell carcinoma (OSCC). Material and

Results

Extracellular expression of MPO and histones was localized within tumor tissue. Significantly lower expression of p67-phox, panRac, and CitH3 was determined in OSCC patients. Considerably lower concentrations of NOX1, NCF2, and DNASE1 in the saliva samples of cancer patients were observed. However, the levels of NOX1, NCF2, and DNASE1 in the serum of patients with cancer were substantially higher. Conclusions: The results obtained from the saliva of cancer patients suggest an impairment of the immunological homeostasis within the oral cavity related to NET formation, the causes of which should be sought in deficient activation of NADPH oxidase.

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