Abstract PR-010: Blinded and meta-analysis validation of an improved serological test for PDAC using the combination of CA19-9 and the sTRA glycan

Improvements in the clinical outcomes of pancreatic cancer patients may be achieved if physicians could identify the disease earlier. Recent studies demonstrated the promise of a biomarker panel is a simple combination between CA19-9 and another marker called sTRA, so named because it detects the sialylated version of the glycan bound by the TRA-1-60 (tumor-related antigen) antibody. The sTRA glycan is structurally related to the CA19-9 antigen and is produced by a different subtype of cancer cells than make CA19-9. We hypothesized that, among patients with PDAC, different patients have plasma elevations in CA19-9 than have plasma elevations in sTRA, and that as a result, a panel comprising the two markers detects more cancers at high specificity (low false-positive rate) than either marker alone. To test this hypothesis, we analyzed the relationships and biomarker performance of CA19-9 and sTRA across seven different datasets, encompassing 729 patient samples collected from four different clinical centers. We tested whether unique elevation occurred for each marker in each dataset, and whether the combination of markers performed better than then individual markers for distinguishing PDAC from healthy subjects and from benign pancreatic disease. We observed complementary elevations of sTRA or CA19-9 in the PDAC patients in each dataset. A two-marker panel composed of CA19-9 and sTRA and a three-marker panel composed of CA19-9 and two versions of the sTRA immunoassay gave statistically significant improvements over CA19-9 across the datasets for distinguishing PDAC from non-PDAC samples (healthy, chronic pancreatitis, pancreatic cyst, and biliary stricture/stones). At 95% specificity, sensitivity was improved from 36-55% across datasets for CA19-9 to 61-67% across datasets for the three-marker panel. The lead panel further showed 95% specificity and 61% sensitivity using blinded calls on another validation set (N = 340). This analysis serves as broad support for an improved serological test for PDAC using the combination of CA19-9 and sTRA. In light of this level of validation, the lead panel could be considered the most promising panel from the currently available information. If further validated using clinical assays, it may be good enough for surveillance among patients with increased risk for PDAC, in combination with follow-up modalities to establish diagnosis. Citation Format: Ying Liu, Ben Staal, Daniel Barnett, Zonglin He, Chongfeng Gao, Mark Hurd, Pamela Bartlett, Aatur Singhi, J. Bradley Morrow, Gregory Cote, Anirban Maitra, Ying Huang, Randall Brand, Brian Haab. Blinded and meta-analysis validation of an improved serological test for PDAC using the combination of CA19-9 and the sTRA glycan [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PR-010.