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...
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creator | 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 |
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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0250539</identifier><identifier>PMID: 34587190</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Animal growth ; Animal models ; Antibodies ; Antigens ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - blood ; Cancer ; Carcinoma, Pancreatic Ductal - blood ; Carcinoma, Pancreatic Ductal - mortality ; Carcinoma, Pancreatic Ductal - pathology ; Case-Control Studies ; Diagnosis ; Female ; Gastrointestinal cancer ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Histochemistry ; Humans ; Immunohistochemistry ; Kidney cancer ; Labeling ; Laboratories ; Lesions ; Male ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Monoamine Oxidase - blood ; Neoplasm Grading ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - blood ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Pancreatitis ; Parametric analysis ; Patients ; Plasma ; Precursors ; Prognosis ; Prospective Studies ; Retrospective Studies ; Surgery ; Survival ; Survival Analysis ; Tissues ; Trauma ; Tumors ; Up-Regulation ; Veterans ; Young Adult</subject><ispartof>PloS one, 2021-09, Vol.16 (9), p.e0250539</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>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 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4e6146686e98fbf5d00fa0419cb6ec3db5dc1ea33f41014a82d7b3b66640ee683</citedby><cites>FETCH-LOGICAL-c692t-4e6146686e98fbf5d00fa0419cb6ec3db5dc1ea33f41014a82d7b3b66640ee683</cites><orcidid>0000-0001-8293-6803 ; 0000-0002-2618-4173</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480607/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480607/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34587190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Su, Gloria H.</contributor><creatorcontrib>Gao, Yasheen</creatorcontrib><creatorcontrib>Wang, Melinda</creatorcontrib><creatorcontrib>Guo, Xiaojia</creatorcontrib><creatorcontrib>Hu, Joanna</creatorcontrib><creatorcontrib>Chen, Tian-Min</creatorcontrib><creatorcontrib>Finn, Sade M B</creatorcontrib><creatorcontrib>Lacy, Jill</creatorcontrib><creatorcontrib>Kunstman, John W</creatorcontrib><creatorcontrib>Cha, Charles H</creatorcontrib><creatorcontrib>Bellin, Melena D</creatorcontrib><creatorcontrib>Robert, Marie E</creatorcontrib><creatorcontrib>Desir, Gary V</creatorcontrib><creatorcontrib>Gorelick, Fred S</creatorcontrib><title>Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Acids</subject><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Animal growth</subject><subject>Animal models</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Cancer</subject><subject>Carcinoma, Pancreatic Ductal - blood</subject><subject>Carcinoma, Pancreatic Ductal - mortality</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Case-Control Studies</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Gastrointestinal cancer</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Histochemistry</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kidney cancer</subject><subject>Labeling</subject><subject>Laboratories</subject><subject>Lesions</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Monoamine Oxidase - blood</subject><subject>Neoplasm Grading</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - blood</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatitis</subject><subject>Parametric analysis</subject><subject>Patients</subject><subject>Plasma</subject><subject>Precursors</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Tissues</subject><subject>Trauma</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>Veterans</subject><subject>Young 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is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4e6146686e98fbf5d00fa0419cb6ec3db5dc1ea33f41014a82d7b3b66640ee683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acids</topic><topic>Adenocarcinoma</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Animal growth</topic><topic>Animal models</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Biological markers</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - 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Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Yasheen</au><au>Wang, Melinda</au><au>Guo, Xiaojia</au><au>Hu, Joanna</au><au>Chen, Tian-Min</au><au>Finn, Sade M B</au><au>Lacy, Jill</au><au>Kunstman, John W</au><au>Cha, Charles H</au><au>Bellin, Melena D</au><au>Robert, Marie E</au><au>Desir, Gary V</au><au>Gorelick, Fred S</au><au>Su, Gloria H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-09-29</date><risdate>2021</risdate><volume>16</volume><issue>9</issue><spage>e0250539</spage><pages>e0250539-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34587190</pmid><doi>10.1371/journal.pone.0250539</doi><tpages>e0250539</tpages><orcidid>https://orcid.org/0000-0001-8293-6803</orcidid><orcidid>https://orcid.org/0000-0002-2618-4173</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2021-09, Vol.16 (9), p.e0250539 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acids Adenocarcinoma Adult Aged Aged, 80 and over Analysis Animal growth Animal models Antibodies Antigens Biological markers Biology and Life Sciences Biomarkers Biomarkers, Tumor - blood Cancer Carcinoma, Pancreatic Ductal - blood Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - pathology Case-Control Studies Diagnosis Female Gastrointestinal cancer Gene Expression Regulation, Neoplastic Genetic aspects Histochemistry Humans Immunohistochemistry Kidney cancer Labeling Laboratories Lesions Male Medical prognosis Medicine Medicine and Health Sciences Middle Aged Monoamine Oxidase - blood Neoplasm Grading Pancreas Pancreatic cancer Pancreatic Neoplasms - blood Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pancreatitis Parametric analysis Patients Plasma Precursors Prognosis Prospective Studies Retrospective Studies Surgery Survival Survival Analysis Tissues Trauma Tumors Up-Regulation Veterans Young Adult |
title | Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma |
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