Abstract
BackgroundPancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specific MMP-generated collagen fragments differentiate PC patients from healthy controls when measured in serum.MethodsThe levels of biomarkers reflecting MMP-mediated degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12a1) collagen were assessed in serum samples from PC patients (n = 15) and healthy controls (n = 33) using well-characterized and validated competitive ELISAs.ResultsThe MMP-generated collagen fragments were significantly elevated in serum from PC patients as compared to controls. The diagnostic power of C1M, C3M, C4M and C4M12 were ≥83% (p < 0.001) and when combining all biomarkers 99% (p < 0.0001).ConclusionsA panel of serum biomarkers reflecting altered MMP-mediated collagen turnover is able to differentiate PC patients from healthy controls. These markers may increase the understanding of mode of action of the disease and, if validated in larger clinical studies, provide an improved and additional tool in the PC setting.
Highlights
Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers
The aim of this study was to investigate whether protein fingerprints of specific matrix metalloproteinase (MMP)-generated collagen protein fragments may differentiate PC patients from healthy controls when measured in serum
MMP-mediated degradation of collagen Levels of MMP-generated fragments of collagen type I, III and IV were significantly elevated in serum from PC patients as compared to controls (Figure 1)
Summary
Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specific MMP-generated collagen fragments differentiate PC patients from healthy controls when measured in serum. Pancreatic cancer (PC) is an aggressive disease with a poor prognosis at time of diagnosis. Due to a lack of specific clinical symptoms, most patients have unresectable primary tumors and/or metastatic spread at the time of diagnosis, resulting in incurative disease. These facts make PC one of the top five most lethal types of cancer with approximately 70% of patients dying within. Desmoplasia is similar to fibrotic tissue and includes proteins such as collagens, fibronectin, proteoglycans and hyaluronic acid
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