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

Chen, Inna M.; Willumsen, Nicholas; Dehlendorff, Christian; Johansen, Astrid Z.; Jensen, Benny Vittrup; Hansen, Carsten Palnæs; Hasselby, Jane Preuss; Bojesen, Stig E.; Pfeiffer, Per; Nielsen, Svend Erik; Holländer, Niels Henrik; Yilmaz, Mette Karen; Karsdal, Morten A.; Johansen, Julia S.

doi:10.1002/ijc.32751

Cited by 47 publications

(47 citation statements)

References 51 publications

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“…The most dominant proteins in the ECM are the collagens, of which there are 28 different types [7]. Our research group has previously demonstrated that collagens and other ECM proteins can be valuable as non-invasive biomarker tools in different cancer forms [8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

Thorlacius-Ussing

Manon‐Jensen

Sun

et al. 2020

Cancers

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Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer. In this study, we describe a competitive ELISA, named PRO-C19, targeting the C-terminus of collagen XIX using a monoclonal antibody. PRO-C19 was measured in serum of patients with a range of cancer types and was elevated in non-small cell lung cancer (NSCLC) (p < 0.0001), small cell lung cancer (p = 0.0081), breast (p = 0.0005) and ovarian cancer (p < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (p = 0.0003) and squamous cell carcinoma (SCC) (p < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (p = 0.0457). PRO-C19 could discriminate between NSCLC and healthy controls (AUROC:0.749 and 0.826 for AD and SCC, respectively) and maintained discriminatory performance in patients of tumor stages I+II (AUROC:0.733 and 0.818 for AD and SCC, respectively). Lastly, we confirmed the elevated type XIX collagen levels using gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) initiatives. In conclusion, type XIX collagen is released into circulation and is significantly elevated in the serum of cancer patients and PRO-C19 shows promise as a cancer biomarker.

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Section: Introductionmentioning

confidence: 99%

Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

Thorlacius-Ussing

Manon‐Jensen

Sun

et al. 2020

Cancers

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“…The migration of stem-cells according to LMW-HA gradient has been documented [98][99][100][101]. An increase in LMW-HA levels may occur in case of non-alcoholic steatohepatitis complicated with fibrosis [102,103] or of pancreatic cancer [104]. Hyaluronan content of the pancreas governs tissue stiffness and pancreatic islet inflammation [105].…”

Section: Nlr Lmw-ha Fatty Pancreasmentioning

confidence: 99%

Levels of Hydrogen Sulphide or Nitric Oxide in Induced Belching are Indicators of Adequate Gastric Voiding

Donatini¹,

Blaye²

2021

J Clin Case Stu

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“…ECM neo-peptides are increasingly investigated as potential predictive and prognostic biomarkers. For example, C3M and PRO-C3 have shown prognostic and predictive value in metastatic breast cancer and pancreas cancer [28][29][30]. Furthermore, a high ratio of type III collagen degradation to formation (C3M/PRO-C3) at baseline predicts overall survival (OS) in patients with metastatic melanoma and advanced pancreas cancer [23,30].…”

Section: Introductionmentioning

confidence: 99%

Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa

et al. 2021

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Background Extensive extracellular matrix (ECM) remodeling is a hallmark of metastatic pancreatic ductal adenocarcinoma (mPDA). We investigated fragments of collagen types III (C3M, PRO-C3), VI (PRO-C6), and VIII (C8-C), and versican (VCANM) in plasma as biomarkers for predicting progression-free survival (PFS) and overall survival (OS) in patients with mPDA treated with pegvorhyaluronidase alfa, a biologic that degrades the ECM component hyaluronan (HA), in a randomized phase 2 study (HALO109-202). Methods HALO109-202 comprised a discovery cohort (Stage 1, n = 94) and a validation cohort (Stage 2, n = 95). Plasma ECM biomarkers were analyzed by ELISAs. Univariate Cox regression analysis and Kaplan–Meier plots evaluated predictive associations between biomarkers, PFS and OS in patients treated with pegvorhyaluronidase alfa plus nab-paclitaxel/gemcitabine (PAG) versus nab-paclitaxel/gemcitabine (AG) alone. Results PFS was improved with PAG vs. AG in Stage 1 patients with high C3M/PRO-C3 ratio (median cut-off): median PFS (mPFS) 8.0 vs. 5.3 months, P = 0.031; HR = 0.40; 95% CI 0.17–0.92). High C3M/PRO-C3 ratio was validated in Stage 2 patients by predicting a PFS benefit of PAG vs. AG (mPFS: 8.8 vs. 3.4 months, P = 0.046; HR = 0.46; 95% CI 0.21–0.98). OS was also improved in patients with high C3M/PRO-C3 ratio treated with PAG vs. AG (mOS 13.8 vs 8.5 months, P = 0.009; HR = 0.35; 95% CI 0.16–0.77). Interestingly, high C3M/PRO-C3 ratio predicted for a PFS benefit to PAG vs. AG both in patients with HA-low tumors (HR = 0.36; 95% CI 0.17–0.79) and HA-high tumors (HR = 0.20; 95% CI 0.06–0.69). Conclusions The C3M/PRO-C3 ratio measuring type III collagen turnover in plasma has potential as a blood-based predictive biomarker in patients with mPDA and provides additional value to a HA biopsy when applied for patient selection. Trial registration: NCT01839487. Registered 25 April 2016

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

Cited by 47 publications

References 51 publications

Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

Levels of Hydrogen Sulphide or Nitric Oxide in Induced Belching are Indicators of Adequate Gastric Voiding

Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa

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