Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients

Abstract

Objectives Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular traps (NETs) markers during the perioperative period from 24 hours before surgery up to 72 hours after curative surgery in cancer patients. Methods We examined the plasma levels of two NETs protein markers (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origins in 29 patients colon, prostate and breast cancer and in 114 healthy individuals (HI). Results The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer (r=0.60 (p<0.001) and r=0.53 (p<0.01), respectively), but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI. Conclusion Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondria dysfunction.