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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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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Adenocarcinoma
Validation Studies
thrombospondin 2
Pancreatic Diseases
ROC Curve
Pancreatitis
Neoplasms
Enzyme-Linked Immunosorbent Assay
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, J., Bamlet, W. R., Oberg, A. L., Chaffee, K. G., Donahue, G., Cao, X. J., ... 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

Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 & CA19-9 blood markers. / Kim, Jungsun; Bamlet, William R.; Oberg, Ann L.; Chaffee, Kari G.; Donahue, Greg; Cao, Xing Jun; Chari, Suresh; Garcia, Benjamin A.; Petersen, Gloria M.; Zaret, Kenneth S.

In: Science Translational Medicine, Vol. 9, No. 398, eaah5583, 12.07.2017.

Research output: Contribution to journalArticle

Kim, J, Bamlet, WR, Oberg, AL, Chaffee, KG, Donahue, G, Cao, XJ, Chari, S, Garcia, BA, Petersen, GM & Zaret, KS 2017, 'Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 & CA19-9 blood markers', Science Translational Medicine, vol. 9, no. 398, eaah5583. https://doi.org/10.1126/scitranslmed.aah5583
Kim, Jungsun ; Bamlet, William R. ; Oberg, Ann L. ; Chaffee, Kari G. ; Donahue, Greg ; Cao, Xing Jun ; Chari, Suresh ; Garcia, Benjamin A. ; Petersen, Gloria M. ; Zaret, Kenneth S. / Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 & CA19-9 blood markers. In: Science Translational Medicine. 2017 ; Vol. 9, No. 398.
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