A blood-based multi marker assay supports the differential diagnosis of early-stage pancreatic cancer

Andreas W. Berger, Daniel Schwerdel, Anke Reinacher-Schick, Waldemar Uhl, Hana Algül, Helmut Friess, Klaus Peter Janssen, Alexander König, Michael Ghadimi, Eike Gallmeier, Detlef K. Bartsch, Michael Geissler, Ludger Staib, Andrea Tannapfel, Alexander Kleger, Alica Beutel, Lucas Alexander Schulte, Marko Kornmann, Thomas J. Ettrich, Thomas Seufferlein

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this limitation. Methods: Prior to surgery plasma levels of thrombospondin-2 (THBS2), which was recently published as a novel biomarker, and CA19-9 from 52 patients with histologically proven PDAC were determined, circulating cell-free (cfDNA) was quantified. 15 patients with side-branch IPMNs without worrisome features and 32 patients with chronic pancreatitis served for comparison. Logit (logistic regression) models were used to test the performance of single biomarkers and biomarker combinations. Results: CA19-9 and THBS2 alone showed comparable c-statistics of 0.80 and 0.73, respectively, improving to 0.87 when combining these two markers. The c-statistic was further increased to 0.94 when combining CA19-9 and THBS2 with cfDNA quantification. This marker combination performed best for all PDAC stages but also for PDACs grouped by stage. The greatest improvement over CA19-9 was seen in the group of stage I PDAC, from 0.69 to 0.90 for the three marker combination. Conclusion:These data establish the combination of CA19-9, THBS2 and cfDNA as a composite liquid biomarker for non-invasive diagnosis of early-stage PDAC.

Original languageEnglish
Pages (from-to)1280-1287
Number of pages8
JournalTheranostics
Volume9
Issue number5
DOIs
StatePublished - 2019

Keywords

  • CA19-9
  • Circulating tumor DNA
  • Liquid biopsy
  • Pancreatic cancer
  • Thrombospondin-2

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