scholarly journals Serum glycoprotein biomarker validation for esophageal adenocarcinoma and application to Barrett’s surveillance

2018 ◽  
Author(s):  
Alok K. Shah ◽  
Gunter Hartel ◽  
Ian Brown ◽  
Clay Winterford ◽  
Renhua Na ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Binding Protein ◽  
Multiple Reaction Monitoring ◽  
Magnetic Bead ◽  
Low Grade ◽  
Complement Factor ◽  
Serum Glycoprotein ◽  
Serum Paraoxonase

SUMMARYBACKGROUND & AIMSEsophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett’s esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for 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 panel for BE surveillance.METHODSSerum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS). The area under receiver operating characteristic curve was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance.RESULTSDifferent glycoforms of complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarker candidates for EAC across both cohorts. A panel of 10 serum glycoproteins accurately discriminated BE patients not requiring intervention [BE+/-low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC]. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 glycoforms were increased with disease progression.CONCLUSIONSFurther prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted. A first-line BE surveillance blood test may be developed based on these findings.AbbreviationsAALAleuria aurantia lectin%CV% Co-efficient of variationAUROCArea under receiver operating characteristics curveBEBarrett’s esophagusBE-HGDBarrett’s esophagus with high-grade dysplasiaBE-IDBarrett’s esophagus which is indefinite for dysplasiaBE-LGDBarrett’s esophagus with low-grade dysplasiaBMIBody mass indexC1QBComplement C1q subcomponent subunit BC2Complement C2C3Complement C3C4BComplement C4-BC4BPAC4b-binding protein alpha chainC4BPBC4b-binding protein beta chainC9Complement component C9CFBComplement factor BCFIComplement factor ICIConfidence intervalCPCeruloplasminEACEsophageal adenocarcinomaEPHAErythroagglutinin from Phaseolus vulgarisFFPEFormalin-fixed, paraffin-embeddedGERDGastroesophageal reflux diseaseGSNGelsolinJACJacalin from Artocarpus integrifoliaLeMBALectin magnetic bead arrayMRM-MSMultiple reaction monitoring-mass spectrometryNPLNarcissus pseudonarcissus lectinNSENon-specialized epitheliumOROdds ratioPGLYRP2N-acetylmuramoyl-L-alanine amidasePON1Serum paraoxonase/arylesterase 1PON3Serum paraoxonase/lactonase 3RBP4Retinol-binding protein 4SERPINA4KallistatinSISStable isotope-labeled internal standard

scholarly journals Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus

2018 ◽  
Vol 17 (12) ◽  
pp. 2324-2334 ◽  
Author(s):  
Alok K. Shah ◽  
Gunter Hartel ◽  
Ian Brown ◽  
Clay Winterford ◽  
Renhua Na ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Serum Glycoprotein

scholarly journals Indications, contraindications and limitations of endoscopic therapy for Barrett’s esophagus and early esophageal adenocarcinoma

2020 ◽  
Vol 13 ◽  
pp. 175628482092420
Author(s):  
Carol Rouphael ◽  
Mythri Anil Kumar ◽  
Madhusudhan R. Sanaka ◽  
Prashanthi N. Thota
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
De Novo ◽  
Eradication Therapy ◽  
Outpatient Setting ◽  
Small Subset ◽  
Low Grade ◽  
Mortality And Morbidity ◽  
Ablation Therapy

Endoscopic eradication therapy (EET) has revolutionized management of Barrett’s esophagus (BE)-associated neoplasia, traditionally treated by esophagectomy, which carries very high mortality and morbidity. EET, usually performed in the outpatient setting, has a safe risk profile. It is indicated in patients with BE with high-grade dysplasia and intramucosal cancer, confirmed, and persistent low-grade dysplasia, and in highly selected cases of non-dysplastic BE and submucosal cancers. Multiple EET modalities are available and can be categorized into two groups: ablation therapies and resection techniques with resection techniques usually reserved for nodular/raised lesions or lesions with suspected neoplasia. Patients usually require multiple ablation sessions with a goal of achieving complete eradication of metaplasia. Despite very good results, EET has its limitations and is not 100% effective: it targets a small subset of patients along the spectrum of BE and esophageal adenocarcinoma, as most patients with esophageal adenocarcinoma remain asymptomatic until the disease has progressed to advanced stages. Post-ablation surveillance is mandatory, as recurrences are common. An area of concern is buried metaplasia reported to occur following ablation therapy and thought to be from de novo growth of metaplastic tissue underneath the neosquamous epithelium, following ablation. The focus of this review article is to present the indications, contraindications and limitations of EET.

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