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Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
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 characte...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480607/ https://www.ncbi.nlm.nih.gov/pubmed/34587190 http://dx.doi.org/10.1371/journal.pone.0250539 |
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author | Gao, Yasheen Wang, Melinda Guo, Xiaojia Hu, Joanna Chen, Tian-min Finn, Sade´ M. B. Lacy, Jill Kunstman, John W. Cha, Charles H. Bellin, Melena D. Robert, Marie E. Desir, Gary V. Gorelick, Fred S. |
author_facet | Gao, Yasheen Wang, Melinda Guo, Xiaojia Hu, Joanna Chen, Tian-min Finn, Sade´ M. B. Lacy, Jill Kunstman, John W. Cha, Charles H. Bellin, Melena D. Robert, Marie E. Desir, Gary V. Gorelick, Fred S. |
author_sort | Gao, Yasheen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8480607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84806072021-09-30 Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma Gao, Yasheen Wang, Melinda Guo, Xiaojia Hu, Joanna Chen, Tian-min Finn, Sade´ M. B. Lacy, Jill Kunstman, John W. Cha, Charles H. Bellin, Melena D. Robert, Marie E. Desir, Gary V. Gorelick, Fred S. PLoS One Research Article 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. Public Library of Science 2021-09-29 /pmc/articles/PMC8480607/ /pubmed/34587190 http://dx.doi.org/10.1371/journal.pone.0250539 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Gao, Yasheen Wang, Melinda Guo, Xiaojia Hu, Joanna Chen, Tian-min Finn, Sade´ M. B. Lacy, Jill Kunstman, John W. Cha, Charles H. Bellin, Melena D. Robert, Marie E. Desir, Gary V. Gorelick, Fred S. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title_full | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title_fullStr | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title_full_unstemmed | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title_short | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
title_sort | renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480607/ https://www.ncbi.nlm.nih.gov/pubmed/34587190 http://dx.doi.org/10.1371/journal.pone.0250539 |
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