The CA19-9 and Sialyl-TRA Antigens Define Separate Subpopulations of Pancreatic Cancer Cells

Daniel Barnett,Galen Hostetter,Brian B Haab,Katie Partyka,Richard R Drake,Ying Liu,Ying Huang,Aatur D Singhi,Huiyuan Tang,Randall E Brand

doi:10.1038/s41598-017-04164-z

Abstract

Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those producing CA19-9. The sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3 separate tissue microarrays covering 38 patients. The morphologies of the cancer cells varied in association with glycan expression. Cells with dual staining of both markers tended to be in well-to-moderately differentiated glands with nuclear polarization, but exclusive sTRA staining was present in small clusters of cells with poor differentiation and large vacuoles, or in small and ill-defined glands. Patients with higher dual-staining of CA19-9 and sTRA had statistically longer time-to-progression after surgery. Patients with short time-to-progression (<2 years) had either low levels of the dual-stained cells or high levels of single-stained cells, and such patterns differentiated short from long time-to-progression with 90% (27/30) sensitivity and 80% (12/15) specificity. The sTRA and CA19-9 glycans define separate subpopulations of cancer cells and could together have value for classifying subtypes of pancreatic adenocarcinoma.

Highlights

One of the difficulties associated with the molecular profiling of pancreatic cancers is heterogeneity in the tumors
The CA19-9 antigen is a tetrasaccharide (Fig. 1A) that can be detected with high specificity using monoclonal antibodies
The central question explored here is whether the cancer cells producing sTRA are different in their locations and characteristics than the cancer cells producing the CA19-9 antigen

Summary

Introduction

One of the difficulties associated with the molecular profiling of pancreatic cancers is heterogeneity in the tumors. In previous research we identified a glycan that is a strong serological biomarker of pancreatic cancer[19] It performed as well as the current best serological biomarker for pancreatic cancer, CA19-9, which detects a glycan, and it was elevated in about half of the patients with low CA19-9, indicating independent regulation. These facts led us to speculate that the glycan, which we call sTRA, is produced by a different subpopulation of cancer cells than produce the CA19-9 antigen. We sought to immunologically detect sTRA and CA19-9 in tumor tissue and test for differences in location, morphology, and molecular expression of the cancer cells that produce each glycan. We asked whether particular glycan levels show an association with the rate of progression of pancreatic cancer

Methods

Results

Conclusion