Two biomarkers measured by enzyme-linked immunosorbent assay, thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), detected pancreatic ductal adenocarcinoma (PDAC) with 98% sensitivity and 87% specificity regardless of stage, and distinguished PDAC from pancreatitis (Sci Transl Med 2017;9:eaah5583). Testing these analytes in patients at risk of PDAC one day might be used to diagnose the disease in early, more treatable stages.
Foundational work for these discoveries began in 2013 when the researchers genetically reprogrammed PDAC cells from a patient with advanced disease into an induced pluripotent stem cell-like cell line. Proteomic analyses as the cell line advanced into pancreatic intraepithelial neoplasia led them to target THBS2. CA19-9 already is used to monitor PDAC, but is not considered appropriate for early-stage diagnosis.
The researchers then assessed THBS2 and CA19-9 through a phase 1 discovery and two phase 2 validation studies, one of the latter involving 81 PDAC patients and 80 healthy controls, and the other including 197 PDAC patients, 140 healthy controls, and 200 patients with non-cancer pancreatic disorders, respectively.
THBS2 concentration of 42 ng/mL and CA19-9 ≥55 U/mL yielded 98% sensitivity and 87% specificity. The authors argued that given PDAC’s low prevalence, a test with high specificity would be particularly valued because of the heightened anxieties and additional diagnostic testing in patients with suspected PDAC. The positive predictive value of the test would be just 0.002 in the general population, but would rise to 0.97 in ever more restrictive at-risk patient groups. Meanwhile, the test’s negative predictive value, 1.0 in the general population, would degrade only to 0.92 in any screening scenario.