Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma.
Details
Serval ID
serval:BIB_E23D953BBA48
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma.
Journal
NPJ precision oncology
ISSN
2397-768X (Print)
ISSN-L
2397-768X
Publication state
Published
Issued date
29/06/2021
Peer-reviewed
Oui
Volume
5
Number
1
Pages
61
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
06/07/2021 10:17
Last modification date
08/08/2024 6:41