Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neo...

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Autores principales:	Michelle R. Goulart, Jennifer Watt, Imran Siddiqui, Rita T. Lawlor, Ahmet Imrali, Christine Hughes, Amina Saad, Joanne ChinAleong, Chris Hurt, Catrin Cox, Roberto Salvia, Alberto Mantovani, Tatjana Crnogorac-Jurcevic, Somnath Mukherjee, Aldo Scarpa, Paola Allavena, Hemant M. Kocher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e6dda48966e7423ba07476657d983905
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spelling	oai:doaj.org-article:e6dda48966e7423ba07476657d9839052021-12-02T16:10:32ZPentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma10.1038/s41698-021-00192-12397-768Xhttps://doaj.org/article/e6dda48966e7423ba07476657d9839052021-06-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00192-1https://doaj.org/toc/2397-768XAbstract Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones and otherwise healthy) donated serum in an ethically approved manner. Serum PTX3 above 4.34 ng/mL has a higher sensitivity (86%, 95% confidence interval (CI): 65–97%) and specificity (86%, 95% CI: 79–91%), positive predictive value (97%) and likelihood ratio (6.05), and is superior when compared to serum CA19-9 and CEA for detection of PDAC. In vitro and ex vivo analyses of PTX3, in human PDAC samples, PSCs, cell lines and transgenic mouse model for PDAC, suggest that PTX3 originates from stromal cells, mainly PSC. In activated PSC, PTX3 secretion could be downregulated by rendering PSC quiescent using all-trans-retinoic acid (ATRA). PTX3 organizes hyaluronan in conjunction with tumor necrosis factor-stimulated gene 6 (TSG-6) and facilitates stellate and cancer cell invasion. In SCALOP clinical trial (ISRCTN96169987) testing chemo-radiotherapy without stromal targeting, PTX3 had no prognostic or predictive role. However, in STARPAC clinical trial (NCT03307148), stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control but not those in whom the disease progresses. PTX3 is a putative stromally-derived biomarker for PDAC which warrants further testing in prospective, larger, multi-center cohorts and within clinical trials targeting stroma.Michelle R. GoulartJennifer WattImran SiddiquiRita T. LawlorAhmet ImraliChristine HughesAmina SaadJoanne ChinAleongChris HurtCatrin CoxRoberto SalviaAlberto MantovaniTatjana Crnogorac-JurcevicSomnath MukherjeeAldo ScarpaPaola AllavenaHemant M. KocherNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Michelle R. Goulart Jennifer Watt Imran Siddiqui Rita T. Lawlor Ahmet Imrali Christine Hughes Amina Saad Joanne ChinAleong Chris Hurt Catrin Cox Roberto Salvia Alberto Mantovani Tatjana Crnogorac-Jurcevic Somnath Mukherjee Aldo Scarpa Paola Allavena Hemant M. Kocher Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
description	Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones and otherwise healthy) donated serum in an ethically approved manner. Serum PTX3 above 4.34 ng/mL has a higher sensitivity (86%, 95% confidence interval (CI): 65–97%) and specificity (86%, 95% CI: 79–91%), positive predictive value (97%) and likelihood ratio (6.05), and is superior when compared to serum CA19-9 and CEA for detection of PDAC. In vitro and ex vivo analyses of PTX3, in human PDAC samples, PSCs, cell lines and transgenic mouse model for PDAC, suggest that PTX3 originates from stromal cells, mainly PSC. In activated PSC, PTX3 secretion could be downregulated by rendering PSC quiescent using all-trans-retinoic acid (ATRA). PTX3 organizes hyaluronan in conjunction with tumor necrosis factor-stimulated gene 6 (TSG-6) and facilitates stellate and cancer cell invasion. In SCALOP clinical trial (ISRCTN96169987) testing chemo-radiotherapy without stromal targeting, PTX3 had no prognostic or predictive role. However, in STARPAC clinical trial (NCT03307148), stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control but not those in whom the disease progresses. PTX3 is a putative stromally-derived biomarker for PDAC which warrants further testing in prospective, larger, multi-center cohorts and within clinical trials targeting stroma.
format	article
author	Michelle R. Goulart Jennifer Watt Imran Siddiqui Rita T. Lawlor Ahmet Imrali Christine Hughes Amina Saad Joanne ChinAleong Chris Hurt Catrin Cox Roberto Salvia Alberto Mantovani Tatjana Crnogorac-Jurcevic Somnath Mukherjee Aldo Scarpa Paola Allavena Hemant M. Kocher
author_facet	Michelle R. Goulart Jennifer Watt Imran Siddiqui Rita T. Lawlor Ahmet Imrali Christine Hughes Amina Saad Joanne ChinAleong Chris Hurt Catrin Cox Roberto Salvia Alberto Mantovani Tatjana Crnogorac-Jurcevic Somnath Mukherjee Aldo Scarpa Paola Allavena Hemant M. Kocher
author_sort	Michelle R. Goulart
title	Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
title_short	Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
title_full	Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
title_fullStr	Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
title_full_unstemmed	Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
title_sort	pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e6dda48966e7423ba07476657d983905
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Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma

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