Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 & CA19-9 blood markers

Jungsun Kim, William R. Bamlet, Ann L. Oberg, Kari G. Chaffee, Greg Donahue, Xing Jun Cao, Suresh Chari, Benjamin A. Garcia, Gloria M. Petersen, Kenneth S. Zaret

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Abstract

Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. A phase 1 discovery study (n = 20), a phase 2a validation study (n = 189), and a second phase 2b validation study (n = 537) revealed that concentrations of plasma thrombospondin-2 (THBS2) discriminated among all stages of PDAC consistently. The receiver operating characteristic (ROC) c-statistic was 0.76 in the phase 1 study, 0.84 in the phase 2a study, and 0.87 in the phase 2b study. The plasma concentration of THBS2 was able to discriminate resectable stage I cancer as readily as stage III/IV PDAC tumors. THBS2 plasma concentrations combined with those for CA19-9, a previously identified PDAC marker, yielded a c-statistic of 0.96 in the phase 2a study and 0.97 in the phase 2b study. THBS2 data improved the ability of CA19-9 to distinguish PDAC from pancreatitis. With a specificity of 98%, the combination of THBS2 and CA19-9 yielded a sensitivity of 87% for PDAC in the phase 2b study. A THBS2 and CA19-9 blood m.

Original languageEnglish (US)
Article numbereaah5583
JournalScience Translational Medicine
Volume9
Issue number398
DOIs
StatePublished - Jul 12 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, J., Bamlet, W. R., Oberg, A. L., Chaffee, K. G., Donahue, G., Cao, X. J., Chari, S., Garcia, B. A., Petersen, G. M., & Zaret, K. S. (2017). Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 & CA19-9 blood markers. Science Translational Medicine, 9(398), [eaah5583]. https://doi.org/10.1126/scitranslmed.aah5583