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Theranostics 2019; 9(5):1280-1287. doi:10.7150/thno.29247 This issue Cite

Research Paper

A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer

Andreas W. Berger^1*, Daniel Schwerdel^1*, Anke Reinacher-Schick², Waldemar Uhl³, Hana Algül⁴, Helmut Friess⁵, Klaus-Peter Janssen⁵, Alexander König⁶, Michael Ghadimi⁷, Eike Gallmeier⁸, Detlef K. Bartsch⁹, Michael Geissler¹⁰, Ludger Staib¹¹, Andrea Tannapfel¹², Alexander Kleger¹, Alica Beutel¹, Lucas-Alexander Schulte¹, Marko Kornmann¹³, Thomas J. Ettrich^1#, Thomas Seufferlein^1✉#

1. Ulm University, Department of Internal Medicine I, Albert-Einstein-Allee 23, 89081 Ulm, Germany
2. Ruhr-University Bochum, Division of Hematology, Oncology and Palliative Care, Gudrunstr. 56, 44791 Bochum, Germany
3. Ruhr-University Bochum, Department of Surgery, Gudrunstr. 56, 44791 Bochum, Germany
4. Technical University Munich, Department of Internal Medicine I, Ismaninger Str. 22, 81675 Munich, Germany
5. Technical University Munich, Department of Surgery, Ismaninger Str. 22, 81675 Munich, Germany
6. University Medical Center Goettingen, Department of Gastroenterology and Gastrointestinal Oncology, Robert-Koch-Str. 40, 37075 Goettingen, Germany
7. University Medical Centre Goettingen, Department of General, Visceral and Paediatric Surgery, Robert-Koch-Str. 40, 37075 Goettingen, Germany
8. Philipps University Marburg, Department of Gastroenterology and Endocrinology, Baldingerstraße, 35043 Marburg, Germany
9. Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Baldingerstrasse, 35041, Marburg, Germany
10. Esslingen Hospital, Department of Internal Medicine, Oncology/Hematology, Gastroenterology, Hirschlandstr. 97, 73730 Esslingen, Germany
11. Esslingen Hospital, Department of General and Visceral Surgery, Hirschlandstr. 97, 73730 Esslingen, Germany
12. Ruhr-University Bochum, Department of Pathology, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
13. Ulm University, Department of General and Visceral Surgery, Albert-Einstein-Allee 23, 89081 Ulm, Germany
* These authors contributed equally to this work.
# These authors jointly supervised this project

✉ Corresponding author: Prof. Dr. Thomas Seufferlein, Email: Thomas.seufferleinde; Phone:+49-731-500-44501; Fax: +49-731-500-44502; Ulm University, Department of Internal Medicine I, Albert-Einstein-Allee 23, 89081 Ulm, Germany.

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.

Keywords: liquid biopsy, pancreatic cancer, circulating tumor DNA, CA19-9, thrombospondin-2

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