Detection of Chemotherapy-resistant Pancreatic Cancer Using a Glycan Biomarker, sTRA. Clin Cancer Res 2021 Jan 01;27(1):226-236
Date
10/24/2020Pubmed ID
33093149Pubmed Central ID
PMC7785673DOI
10.1158/1078-0432.CCR-20-2475Scopus ID
2-s2.0-85100339220 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
PURPOSE: A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We hypothesized that a glycan biomarker for PDACs called sialylated tumor-related antigen (sTRA) could be used for this purpose.
EXPERIMENTAL DESIGN: We tested for differences between PDACs classified by glycan expression in multiple systems: sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from human subjects.
RESULTS: The sTRA-expressing models tended to have stem-like gene expression and the capacity for mesenchymal differentiation, in contrast to the nonexpressing models. The sTRA cell lines also had significantly increased resistance to seven different chemotherapeutics commonly used against pancreatic cancer. Patients with primary tumors that were positive for a gene expression classifier for sTRA received no statistically significant benefit from adjuvant chemotherapy, in contrast to those negative for the signature. In another cohort, based on direct measurements of sTRA in tissue microarrays, the patients who were high in sTRA again had no statistically significant benefit from adjuvant chemotherapy. Furthermore, a blood plasma test for the sTRA glycan identified the PDACs that showed rapid relapse following neoadjuvant chemotherapy.
CONCLUSIONS: This research demonstrates that a glycan biomarker could have value to detect chemotherapy-resistant PDAC in clinical settings. This capability could aid in the development of stratified treatment plans and facilitate biomarker-guided trials targeting resistant PDAC.
Author List
Gao C, Wisniewski L, Liu Y, Staal B, Beddows I, Plenker D, Aldakkak M, Hall J, Barnett D, Gouda MK, Allen P, Drake R, Zureikat A, Huang Y, Evans D, Singhi A, Brand RE, Tuveson DA, Tsai S, Haab BBAuthors
Mohammed Aldakkak MD Assistant Professor in the Surgery department at Medical College of WisconsinDouglas B. Evans MD Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antigens, Tumor-Associated, CarbohydrateAntineoplastic Agents
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Cell Line, Tumor
Disease-Free Survival
Drug Resistance, Neoplasm
Humans
Inhibitory Concentration 50
Liquid Biopsy
Neoplasm Recurrence, Local
Pancreatic Neoplasms
Polysaccharides
Risk Assessment
