Abstract
We postulate that a significant part of nuclear circulating cell-free DNA (cirDNA) originates in the degradation of neutrophil extracellular traps (NETs). In this study, we examined the plasma level of two markers of NETs formation (myeloperoxidase (MPO) and neutrophil elastase (NE)), as well as cirDNA levels in 219 patients with a metastatic colorectal cancer (mCRC) at initial diagnosis, and in 114 healthy individuals (HI). We found that in mCRC patients the plasma content of these three analytes was (i) highly correlated, and (ii) all statistically different (P<0.0001) than in HI (N=114). Data revealed that, in mCRC patients, a strong fraction of cirDNA derived from NETs. Receiver operating characteristic (ROC) analysis revealed the high potential of these NETs markers to distinguish between plasma from mCRC patients and from HI, given that it showed 0.88, 0.86, 0.84 and 0.95 AUC values for NE, MPO, cirDNA and NE+MPO+cirDNA, respectively. In addition, a high association of anti-phospholipid (anticardiolipin) levels with NE, MPO, and cirDNA plasma concentrations in mCRC patients suggested that NETosis might be a critical factor in the immunological response/phenomena linked to tumor progression.
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