Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach

The oncologist

article

Tessa Y.S. Le Large¹  Nicole C.T. van Grieken⁴  Barbara M. Zonderhuis¹  Freek Daams¹  Hanneke W.M. van Laarhoven³  Maarten F. Bijlsma⁵  Connie R. Jimenez²  Elisa Giovannetti²  Geert Kazemier¹  Laura L. Meijer¹  Rosita Paleckyte²  Lenka N.C. Boyd¹  Bart Kok¹  Thomas Wurdinger⁷  Tim Schelfhorst²  Sander R. Piersma²  Thang V. Pham² 

[1] Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University;Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University;Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam;Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University;Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam;Cancer Pharmacology Lab, Associazione Italiana per la Ricerca sul Cancro (AIRC) Start-Up Unit, University of Pisa;Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University

关键词: Pancreatic cancer;    Distal cholangiocarcinoma;    Diagnostic biomarkers;    Thrombospondin-2;    Proteomics;   

DOI  :  10.1634/theoncologist.2019-0680

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Minimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome. Materials and Methods Secretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19-9 (CA19-9) were validated by enzyme-linked immunosorbent assay in plasma from patients with PDAC ( n = 82), dCCA ( n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power. Results In tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin-2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs ( p < .001, AUC = 0.844). Combined expression of THBS2 and CA19-9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early- and late-stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19-9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin. Conclusion Our proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19-9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD. Implications for Practice The combined plasma expression of thrombospondin-2 and carbohydrate antigen 19-9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.

【 授权许可】

CC BY|CC BY-NC