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 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.

Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A

“…Patients with PDAC demonstrated significantly lower levels of vitamin A, as measured previously in other studies [81, 82]. An inverse correlation between serum pentraxin 3, a protein associated with local inflammation, and VA levels was found in this study, andRA treatment reducesthe PTX3 protein level [81].…”

Review of Immunohistochemistry Biomarkers in Pancreatic Cancer Diagnosis

“…Predictive positive value was represented in three studies (17.6%), including Goulart et al. ( 16 ), Kaur et al. ( 24 ), and Ibrahim and Abouhashem ( 28 ).…”

“…On assessing positive expression of IHC biomarkers in pancreatic cancer tissue, two (11.8%) out of the 17 included studies, comprising Goulart et al. ( 16 ) and Seifert et al. ( 17 ), did not present IHC scores or thresholds for positivity.…”

Metastatic pancreatic cancer: Mechanisms and detection (Review)

“…PTX3 levels in blood samples from patients with PDAC, healthy volunteers and subjects with other non-cancerous diseases of the pancreas were measured by ELISA and patients with PDAC had significantly higher serum levels of PTX3 than patients with intraductal papillary myxoma or CP, and the sensitivity and specificity of PTX3 in detecting PDAC were better than those of serum CA19-9 and carcinoembryonic antigen. Goulart et al ( 96 ) advocated that PTX3 is a putative stromal-derived biomarker for PDAC, which warrants further testing in larger, prospective, multi-center cohorts and within clinical trials targeting stroma.…”