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

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.

Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor

“…Subpopulations expressing both markers were part of well differentiated and mucin-secreting pancreatic adenocarcinomas, whereas those expressing just one were often poorly differentiated and vacuolated and never mucin-secreting. In addition, the authors observed cases displaying sometimes more than one subpopulation in the same tumor [44]. A heterogeneous distribution of CA 19-9 expression in GBC could explain our findings, especially considering that the clones were isolated from malignant ascites, characterized by containing a heterogeneous group of tumor cells.…”

The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis

“…In the blood of patients with pancreatic cancer, we previously detected the glycans primarily on the mucins MUC1, MUC5AC, and MUC16, and more rarely on MUC5B and MUC3A (7,13,21). We further showed that the cancer cells producing CA19-9 are separate from those producing sTRA (8). If the cancer cells secrete the antigens accordingly ( Fig.…”

“…Another glycan, referred to as sTRA, was elevated in up to half of the patients with low CA19-9, with very low false-positive rates (7). In subsequent research, we found that the cells producing sTRA are different in location, morphologies, and molecular characteristics than the cells producing CA19-9 (8). The above findings suggested that the sTRA glycan would be a serological biomarker for pancreatic cancer that could improve upon CA19-9.…”

Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors

“…It has been shown that spatially and morphologically distinct subsets of pancreatic cancer cells expressed S-Lc 4 (here denoted sTRA) or the CA19-9 antigen (18,42). Well-differentiated ductal pancreatic adenocarcinomas typically expressed both glycans, whereas just one of the markers was expressed by poorly differentiated tumors.…”