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

Goulart, Michelle R., Watt, Jennifer, Siddiqui, Imran, Lawlor, Rita T., Imrali, Ahmet, Hughes, Christine, Saad, Amina, ChinAleong, Joanne, Hurt, Chris ORCID: https://orcid.org/0000-0003-1206-8355, Cox, Catrin, Salvia, Roberto, Mantovani, Alberto, Crnogorac-Jurcevic, Tatjana, Mukherjee, Somnath, Scarpa, Aldo, Allavena, Paola and Kocher, Hemant M. 2021. Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma. npj Precision Oncology 5 (1) , 61. 10.1038/s41698-021-00192-1

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Research
ISSN:	2397-768X
Funders:	CRUK
Date of First Compliant Deposit:	7 July 2021
Date of Acceptance:	25 May 2021
Last Modified:	08 May 2023 18:49
URI:	https://orca.cardiff.ac.uk/id/eprint/142367

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