Research ArticleCancer

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

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Science Translational Medicine  12 Jul 2017:
Vol. 9, Issue 398, eaah5583
DOI: 10.1126/scitranslmed.aah5583

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Getting a head start on pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to a lack of diagnostics for detecting early-stage disease. Kim et al. genetically reprogrammed late-stage human PDAC cells to a stem cell–like state, enabling the reprogrammed cells to recapitulate human PDAC progression and revealing secreted candidate markers of early-stage disease. The protein thrombospondin-2 (THBS2) was screened against 746 cancer and control human plasma samples in a multiphase study. The authors report that, THBS2, in combination with the marker CA19-9, boosts detection of the early stages of PDAC in high-risk human populations.

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 marker panel measured with a conventional ELISA may improve the detection of patients at high risk for PDAC.

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