Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer

• Published in: International journal of cancer 2020-05, Vol.146 (10), p.2913-2922
• Main Authors: Chen, Inna M., Willumsen, Nicholas, Dehlendorff, Christian, Johansen, Astrid Z., Jensen, Benny V., Hansen, Carsten P., Hasselby, Jane P., Bojesen, Stig E., Pfeiffer, Per, Nielsen, Svend E., Holländer, Niels H., Yilmaz, Mette K., Karsdal, Morten, Johansen, Julia S.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenoma; Benign; Biliary tract; biomarkers; Blood flow; Blood pressure; Cancer; Collagen; collagen type III; diagnostic biomarker; Fluid flow; hyaluronan; Hyaluronic acid; Medical research; Metastases; Pancreatic cancer; Pancreatitis; Peritoneum; prognostic biomarker; PRO‐C3; Stroma; Survival
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32751

Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. The aim of this biomarker study was to determine the clinical utility of serum HA and the propeptide of type III collagen (PRO‐C3) in patients with PC. A cohort from the Danish BIOPAC study (NCT03311776) including patients with histologically confirmed pancreatic ductal adenocarcinoma (n = 809), ampullary carcinoma (n = 44), distal biliary tract cancer (n = 31), chronic pancreatitis (n = 15), intraductal papillary mucinous neoplasm (n = 41), duodenal adenoma (n = 7) and no cancer (n = 25). Healthy controls were available for serum HA (n = 141) and PRO‐C3 (n = 8). The main outcome was overall survival (OS) of patients with PC in relation to pretreatment serum HA and PRO‐C3 levels. Patients with PC had higher baseline serum HA and PRO‐C3 than healthy subjects and patients with benign conditions. Pretreatment serum baseline HA and PRO‐C3 in patients with PC were associated with poorer survival and PRO‐C3 remained prognostic also after adjusting for age, performance status, stage, the presence of liver and peritoneum metastasis, and CA19‐9. Detection of HA and PRO‐C3 may be useful in differentiating between malignant and benign pancreatic conditions. Serum HA and PRO‐C3 were prognostic for OS in patients with PC. What's new? Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. In this biomarker study, high levels of serum HA and type III collagen propeptide (PRO‐C3) were associated with short overall survival. Serum HA and PRO‐C3 levels were higher in PC patients than in patients with benign conditions. The findings warrant further exploration to help clarify links between HA, collagen type III, and PC. Moreover, they point to serum PRO‐C3 as a potential prognostic marker in patients with PC.