In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-29), p. e0250539-
Abstract:
Dysregulated expression of the secretory protein renalase can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized renalase expression in premalignant and malignant PDAC tissue and investigated whether plasma renalase levels corresponded to clinical PDAC characteristics. Renalase immunohistochemistry was used to determine the presence and distribution of renalase in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues. Associations between pretreatment plasma renalase and PDAC clinical status were assessed in patients with varied clinical stages of PDAC and included tumor characteristics, surgical resection in locally advanced/borderline resectable PDAC, and overall survival. Data were retrospectively obtained and correlated using non-parametric analysis. Little to no renalase was detected by histochemistry in the normal pancreatic head in the absence of abdominal trauma. In chronic pancreatitis, renalase immunoreactivity localized to peri-acinar spindle-shaped cells in some samples. It was also widely present in PDAC precursor lesions and PDAC tissue. Among 240 patients with PDAC, elevated plasma renalase levels were associated with worse tumor characteristics, including greater angiolymphatic invasion (80.0% vs. 58.1%, p = 0.012) and greater node positive disease (76.5% vs. 56.5%, p = 0.024). Overall survival was worse in patients with high plasma renalase levels with median follow-up of 27.70 months vs. 65.03 months (p 〈 0.001). Renalase levels also predicted whether patients with locally advanced/borderline resectable PDAC underwent resection (AUC 0.674; 95%CI 0.42–0.82, p = 0.04). Overall tissue renalase was increased in both premalignant and malignant PDAC tissues compared to normal pancreas. Elevated plasma renalase levels were associated with advanced tumor characteristics, decreased overall survival, and reduced resectability in patients with locally advanced/borderline resectable PDAC. These studies show that renalase levels are increased in premalignant pancreatic tissues and that its levels in plasma correspond to the clinical behavior of PDAC.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0250539
DOI:
10.1371/journal.pone.0250539.g001
DOI:
10.1371/journal.pone.0250539.g002
DOI:
10.1371/journal.pone.0250539.g003
DOI:
10.1371/journal.pone.0250539.g004
DOI:
10.1371/journal.pone.0250539.g005
DOI:
10.1371/journal.pone.0250539.g006
DOI:
10.1371/journal.pone.0250539.t001
DOI:
10.1371/journal.pone.0250539.t002
DOI:
10.1371/journal.pone.0250539.t003
DOI:
10.1371/journal.pone.0250539.t004
DOI:
10.1371/journal.pone.0250539.t005
DOI:
10.1371/journal.pone.0250539.t006
DOI:
10.1371/journal.pone.0250539.s001
DOI:
10.1371/journal.pone.0250539.s002
DOI:
10.1371/journal.pone.0250539.s003
DOI:
10.1371/journal.pone.0250539.s004
DOI:
10.1371/journal.pone.0250539.s005
DOI:
10.1371/journal.pone.0250539.s006
DOI:
10.1371/journal.pone.0250539.s007
DOI:
10.1371/journal.pone.0250539.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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