Data from Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19-9 Reference Ranges

AbstractPurpose: CA19-9 synthesis is influenced by common variants in the fucosyltransferase (FUT) enzymes FUT3 and FUT2. We developed a clinical test to detect FUT variants and evaluated its diagnostic performance for pancreatic ductal adenocarcinoma (PDAC). Experimental Design: A representative set of controls from the Cancer of the Pancreas Screening study was identified for each FUT functional group. Diagnostic sensitivity was determined first in a testing set of 234 PDAC cases, followed by a 134-case validation set, all of whom had undergone resection with curative intent without neoadjuvant therapy. Tumor marker gene testing was performed in the Johns Hopkins Molecular Diagnostic Laboratory. CA19-9 levels were measured in the Hopkins Clinical Chemistry lab. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative ability of CA19-9 alone versus with the gene test. Results: Applying the CA19-9 standard cutoff (th percentile cut-offs according to each individual’s FUT group, (3, 34.9, 41.8, and 89.2, for the FUT3-null, FUT-low, FUT-intermediate, and FUT-high groups, respectively), yielded a diagnostic sensitivity for CA19-9 in the first set of cases of 66.7%, 65.7% in the validation set, at 98.9% specificity. ROC analysis for CA19-9 alone yielded an area under the curve (AUC) of 0.84; with the tumor marker gene test, AUC improved to 0.92 (p