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

Abstract

PURPOSE:

The CA19-9 biomarker is elevated in a substantial group of patients with pancreatic ductal adenocarcinoma (PDAC), but not enough to be reliable for the detection or diagnosis of the disease. We hypothesized that a glycan called sTRA (sialylated tumor-related antigen) is a biomarker for PDAC that improves upon CA19-9.

EXPERIMENTAL DESIGN:

We examined sTRA and CA19-9 expression and secretion in panels of cell lines, patient-derived xenografts, and primary tumors. We developed candidate biomarkers from sTRA and CA19-9 in a training set of 147 plasma samples and used the panels to make case-control calls, based on predetermined thresholds, in a 50-sample validation set and a blinded, 147-sample test set.

RESULTS:

The sTRA glycan was produced and secreted by pancreatic tumors and models that did not produce and secrete CA19-9. Two biomarker panels improved upon CA19-9 in the training set, one optimized for specificity, which included CA19-9 and 2 versions of the sTRA assay, and another optimized for sensitivity, which included 2 sTRA assays. Both panels achieved statistical improvement (P < 0.001) over CA19-9 in the validation set, and the specificity-optimized panel achieved statistical improvement (P < 0.001) in the blinded set: 95% specificity and 54% sensitivity (75% accuracy), compared with 97%/30% (65% accuracy). Unblinding produced further improvements and revealed independent, complementary contributions from each marker.

CONCLUSIONS:

sTRA is a validated serological biomarker of PDAC that yields improved performance over CA19-9. The new panels may enable surveillance for PDAC among people with elevated risk, or improved differential diagnosis among patients with suspected pancreatic cancer.

• Authors: Ben Staal, Ying Liu, Daniel Barnett, Peter Hsueh, Zonglin He, ChongFeng Gao, Katie Partyka, Mark W Hurd, Aatur D Singhi, Richard R Drake, Ying Huang, Anirban Maitra, Randall E Brand, Brian B Haab
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 9 Pg. 2745-2754 (05 01 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 30617132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Validation Study)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Antigens, Tumor-Associated, Carbohydrate
• Biomarkers, Tumor
• CA-19-9 Antigen
• N-Acetylneuraminic Acid

Topics

• Aged
• Animals
• Antigens, Tumor-Associated, Carbohydrate (blood)
• Biomarkers, Tumor (blood)
• CA-19-9 Antigen (blood)
• Carcinoma, Pancreatic Ductal (blood, diagnosis)
• Case-Control Studies
• Female
• Follow-Up Studies
• Humans
• Male
• Mice
• Middle Aged
• N-Acetylneuraminic Acid (chemistry)
• Pancreatic Neoplasms (blood, diagnosis)
• Prognosis
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays