Cross-species antibody microarray interrogation identifies a 3-protein panel of plasma biomarkers for early diagnosis of pancreas cancer

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, and its incidence is on the rise. Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA at its earliest stages. To discover early biomarkers of PDA, we evaluat...

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Bibliographic Details
Published in:Clinical cancer research 2015-04, Vol.21 (7), p.1764-1771
Main Authors: Mirus, Justin E, Zhang, Yuzheng, Li, Christopher I, Lokshin, Anna E, Prentice, Ross L, Hingorani, Sunil R, Lampe, Paul D
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Area Under Curve
Biomarkers, Tumor - blood
Carcinoma, Pancreatic Ductal - blood
Carcinoma, Pancreatic Ductal - diagnosis
Early Detection of Cancer - methods
Female
Humans
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Microarray Analysis
Middle Aged
Pancreatic Neoplasms - blood
Pancreatic Neoplasms - diagnosis
ROC Curve
Sensitivity and Specificity
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Summary:Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, and its incidence is on the rise. Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA at its earliest stages. To discover early biomarkers of PDA, we evaluated the circulating proteome in murine preinvasive and invasive plasma samples and human prediagnostic and diagnostic samples. Using a customized antibody microarray platform containing >4,000 features, we interrogated plasma samples spanning preinvasive and invasive disease from a highly faithful mouse model of PDA. In parallel, we mined prediagnostic plasma from women in the Women's Health Initiative (WHI) who would later succumb to PDA together with matched, cancer-free control samples. Samples collected after an establishing diagnosis of PDA were also interrogated to further validate markers. We identified ERBB2 and TNC in our cross-species analyses, and multiple antibodies identified ESR1 in prediagnostic plasma from people that succumb to PDA. This 3-marker panel had an AUC of 0.86 (95% confidence interval [CI], 0.76-0.96) for the diagnostic cohort that increased to 0.97 (95% CI, 0.92-1.0) with CA19-9 included. The 3-marker panel also had an AUC of 0.68 (95% CI, 0.58-0.77) for the prediagnostic cohort. We identified potential disease detection markers in plasma up to 4 years before death from PDA with superior performance to CA19-9. These markers might be especially useful in high-risk cohorts to diagnose early, resectable disease, particularly in patients that do not produce CA19-9.
ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.ccr-13-3474