Circulating necroptosis markers in chronic pancreatitis and pancreatic cancer: Associations with diagnosis and prognostic factors.

[OBJECTIVES] Necroptosis, a programmed inflammatory cell death, is implicated in the pathogenesis of pancreatitis and its potential progression to pancreatic ductal adenocarcinoma (PDAC), but its role remains unclear. We compared plasma levels of necroptosis-related markers - mixed lineage kinase domain-like protein (MLKL), interleukin (IL)-33, and its soluble receptor (sST2)- in patients with chronic pancreatitis (CP), PDAC, and healthy controls (HC), to explore their diagnostic and prognostic significance.

[METHODS] Plasma was collected from patients pre-procedurally (PDAC, n = 82; CP, n = 25) and from HC (n = 39), and studied by ELISA. Clinical and routine laboratory data were collected, and pancreas was defined as soft or non-soft based on intraoperative or imaging findings. Mann-Whitney U test, Spearman correlation coefficients, ROC analysis were used for statistical analysis.

[RESULTS] Plasma MLKL was lower in patients with CP than in other groups (p < 0.001) and PDAC patients treated with upfront surgery (PDACUS, n = 65) had lower MLKL than HC (p = 0.035). MLKL differentiated CP from PDACUS (AUC 0.83, p < 0.001). sST2 levels were significantly lower in HC than in other groups (p < 0.001) and in PDAC patients with a soft pancreas compared with non-soft (p < 0.005). In Lewis antigen positive PDACUS (n = 59), sST2 had positive correlations with CA19-9 measured concurrently and after 1 month, and with CEA measured after 1 or 6 months.

[CONCLUSIONS] Circulating levels of MLKL are lower in patients with CP than PDAC. Elevated sST2 levels are associated with pancreatic diseases. Further studies are required to show whether MLKL and sST2 could be useful biomarkers in evaluating pancreatic diseases.