Prof. Hemant Kocher, MBBS, MS, MD, FRCS from the Queen Mary University of London speaks about Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma.
Link to Article:
https://www.nature.com/articles/s41698-021-00192-1
Abstract:
There are no good diagnostic indicators for pancreatic ductal adenocarcinoma (PDAC), which is characterized by thick desmoplastic stroma laid down by pancreatic stellate cells (PSC). In an ethically authorized way, a multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones, and otherwise healthy) contributed serum. When compared to serum CA19-9 and CEA, serum PTX3 above 4.34 ng/mL has a higher sensitivity (86 percent, 95 percent confidence interval (CI): 65"“97 percent ) and specificity (86 percent, 95 percent CI: 79"“91 percent ), positive predictive value (97 percent ), and likelihood ratio (6.05), and is superior in detecting PDAC. In vitro and ex vivo studies of PTX3 in human PDAC samples, PSCs, cell lines, and a PDAC transgenic mice model show that PTX3 is produced by stromal cells, mostly PSC. By utilizing all-trans-retinoic acid to make activated PSC quiescent, PTX3 secretion may be reduced (ATRA). In collaboration with tumor necrosis factor-stimulated gene 6 (TSG-6), PTX3 organizes hyaluronan and promotes stellate and cancer cell invasion. PTX3 exhibited no prognostic or predictive value in the SCALOP clinical study (ISRCTN96169987), which tested chemo-radiotherapy without stromal targeting. However, in the STARPAC clinical study (NCT03307148), stromal modulation by ATRA is associated with a serum PTX3 response even at the first dosage in patients who go on to show disease control, but not in those who advance. PTX3 is a potential stromally-derived biomarker for PDAC that should be investigated further in prospective, bigger, multi-center cohorts and clinical studies focusing on the stroma.
Introduction:
Up to 90% of patients with pancreatic ductal adenocarcinoma (PDAC) arrive with advanced disease as a result of delayed diagnosis1, owing to a lack of distinct symptoms and signs early in the illness, which is worsened by a lack of particular biomarkers to help early detection2. CA19-9, the most commonly used blood biomarker for PDAC in clinical practice, has a medium sensitivity (41"“86%) and specificity (33"“100%)2,3. The combination of CEA and CA19-9 has been suggested to improve diagnostic accuracy4, although this has not been confirmed3. As a result, no accurate and practically relevant biomarkers for early diagnosis of PDAC exist at this time, however, a panel of urine biomarkers is making inroads into large-scale clinical trials5.
The pancreatic stellate cells (PSC)6,7,8 lay down an intensive desmoplastic stroma, which is characteristic of PDAC. Our previous research has demonstrated that targeting active PSC with the pleiotropic drug All-trans Retinoic Acid (ATRA) causes them to go dormant9. Pentraxin 3 (PTX3) transcripts are down-regulated when PSC is rendered quiescent, according to a gene-expression microarray. We hypothesized that serum PTX3 may serve as a proxy for desmoplasia and, hence, PDAC.
A sample size of 260 was determined in pilot research comparing blood PTX3 levels in patients with PDAC to age/gender-matched controls (Fig. 1A) and nomograms for diagnostic tests10. This was based on a 50% prevalence (P0.5) assumption in our population (cancer vs other pancreatic illnesses or healthy controls), an expected accuracy (W0.05), and a confidence interval of 5% (CI = 0.05, z = 1.96) with a sensitivity of 90% (SN = 0.9) and specificity of 90% (SP = 0.9).