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Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus
- Publication Year :
- 2018
- Publisher :
- The American Society for Biochemistry and Molecular Biology, 2018.
-
Abstract
- Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance of BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and the United States (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention (BE± low grade dysplasia) from those requiring intervention (BE with high grade dysplasia (BE-HGD) or EAC) with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed toward EAC, levels of serum C9 were significantly (p < 0.05) increased with disease progression in EPHA (erythroagglutinin from Phaseolus vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Esophageal Neoplasms
Biopsy
Adenocarcinoma
Biochemistry
Gastroenterology
Asymptomatic
Mass Spectrometry
Analytical Chemistry
Cohort Studies
Diagnosis, Differential
03 medical and health sciences
Barrett Esophagus
0302 clinical medicine
Internal medicine
medicine
Blood test
Humans
Public Health Surveillance
Esophagus
Molecular Biology
Gelsolin
Aged
medicine.diagnostic_test
business.industry
Aryldialkylphosphatase
Research
Australia
Middle Aged
medicine.disease
Complement C9
PON1
United States
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Barrett's esophagus
Area Under Curve
Multivariate Analysis
Biomarker (medicine)
Female
medicine.symptom
business
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6da7161f27bd4538388ac7f8ee91692b