Intraductal papillary mucinous neoplasm (IPMN) can progress into malignant pancreatic
cancer, posing challenges in accurately assessing the risk of malignancy. While the
nucleotide‐binding oligomerization domain (NOD)‐like receptor pyrin domain containing
3 (NLRP3) inflammasome pathway's role in pancreatic ductal adenocarcinoma (PDAC) has
been extensively studied, its implications in IPMN remain unexplored. This study aimed
to investigate the prognostic significance of NLRP3 inflammasome‐related proteins
across IPMN subtypes and their associations with tumor characteristics, with a secondary
focus on comparing expression patterns in IPMN and PDAC. A cohort of 187 patients
(100 IPMN and 87 PDAC) underwent high‐dimensional histopathological imaging using
the multiplexed immunohistochemical consecutive staining on single slide method and
a semi‐automated image analysis workflow. Expression levels of NLRP3, apoptosis‐associated
speck‐like protein containing a caspase‐recruitment domain (ASC), caspase‐1, interleukin‐1
beta, interleukin‐18 (IL‐18), interleukin‐1 receptor antagonist, and interleukin‐18
binding protein (IL‐18BP) were evaluated and compared between IPMN and PDAC samples.
The relationships between protein expression and tumor characteristics were examined.
Principal component analysis distinguished between intestinal and nonintestinal clusters
based on NLRP3‐associated proteins. Lower IL‐18 expression was linked to the intestinal
subtype, while higher caspase‐1 was linked to the pancreatobiliary subtype. Elevated
caspase‐1 and ASC expression were associated with invasiveness in IPMN. No significant
correlation was found between the examined proteins and later‐stage tumor characteristics
in invasive cases. The IL‐18/IL‐18BP ratio was an independent prognostic factor in
invasive IPMN. Our findings highlight the prognostic significance of IL‐18 and the
IL‐18/IL‐18BP ratio in invasive IPMNs. These results point to a complex regulation
of NLRP3 inflammasome proteins, especially effector cytokines, in pancreatic neoplasms,
which are strongly linked to subtype and prognosis.
