TY - JOUR
T1 - The Stra plasma biomarker
T2 - Blinded validation of improved accuracy over CA19-9 in pancreatic cancer diagnosis
AU - Staal, Ben
AU - Liu, Ying
AU - Barnett, Daniel
AU - Hsueh, Peter
AU - He, Zonglin
AU - Gao, Chong Feng
AU - Partyka, Katie
AU - Hurd, Mark W.
AU - Singhi, Aatur D.
AU - Drake, Richard R.
AU - Huang, Ying
AU - Maitra, Anirban
AU - Brand, Randall E.
AU - Haab, Brian B.
N1 - Funding Information:
We thank the VARI Confocal Microscopy and Quantitative Imaging core for assistance with fluorescence image acquisition on the tissue samples; and Luke Wisniewski at VARI for assistance preparing the cell cultures. NCI: U01 CA152653 (to B.B. Haab, R.E. Brand, Y. Huang); U01 CA200466 (to R.E. Brand); U01 CA200468 (to A. Maitra); U01 CA168896 (to B.B. Haab, R.E. Brand, Y. Huang); U01 CA196403 (to A. Maitra); P30 CA138313 (to R.R. Drake).
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-18-3310
DO - 10.1158/1078-0432.CCR-18-3310
M3 - Article
C2 - 30617132
AN - SCOPUS:85065546486
SN - 1078-0432
VL - 25
SP - 2745
EP - 2754
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -