The sTRA glycan is complementary to CA19-9 as a serologic biomarker of pancreatic cancer

The CA19-9 biomarker is elevated in a substantial group of patients with pancreatic cancer, but not enough to be reliable for detection, diagnosis, or monitoring of the disease. We hypothesized that a glycan called sTRA complements CA19-9, and that the two biomarkers in combination provide added information over either biomarker individually. As an individual marker, the sTRA assay performed equivalently with CA19-9 for distinguishing cancers from benign pancreatic diseases, but in combination, CA19-9 and sTRA showed exclusive elevations in significantly different groups of patients. Using high-specificity cutoffs giving one false-positive detection in each marker, sTRA was elevated in 34/46 (74%) patients with low CA19-9 in stage III/IV cancers and 28/70 (40%) with low CA19-9 in stage I/II cancers. A three-marker panel consisting of CA19-9 and two versions of the sTRA assay gave 81% sensitivity and 88% specificity (84% accuracy) in a training set of 72 stage I-IV cancers and 75 benign disease controls, compared to 57% sensitivity and 92% specificity (75% accuracy) for CA19-9 alone. The application of the fixed three-marker classifier to a test set of 25 cancers and 25 benign controls gave 80% sensitivity and 84% specificity, compared to 56% sensitivity and 96% specificity for CA19-9 alone. In an analysis of patient-matched tumor tissue and plasma samples, we found that the tumors secreting both sTRA and CA19-9 into the blood tended to be conventional PDAC with well-to-moderate differentiation and heavy marker staining in the ductal lumens, but the tumors secreting only sTRA showed sTRA staining in glands with extremely large and unpolarized nuclei and vacuolated or foamy cytoplasm. Those without plasma elevations in either marker did not have glandular features of typical adenocarcinoma. Surprisingly, about half of the patients without plasma elevations of CA19-9 nevertheless showed strong tumor staining. Such tumors expressed CA19-9 mostly in poorly differentiated patches of cells with compact nuclei and cytoplasm. Thus, sTRA and CA19-9 are complementary serologic biomarkers that together could increase the diagnostic accuracy for PDAC and potentially identify distinct subgroups of tumors. Citation Format: Ying Liu, Daniel Barnett, Ben Staal, Ying Huang, Katie Partyka, Herbert Zeh, Aatur Singhi, Richard R. Drake, Randall E. Brand, Brian B. Haab. The sTRA glycan is complementary to CA19-9 as a serologic biomarker of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4624.