Abstract 4942: Towards a screening blood test for esophageal adenocarcinoma

Abstract

Abstract BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has been rapidly increasing globally. The majority of EAC cases are diagnosed at late stages leading to poor 5-year survival of <20%. Monitoring programs for patients with the metaplastic condition, Barrett's esophagus (BE) involves endoscopy with biopsy. However, the cost-effectiveness is limited by the low rate of progression to cancer and expense of the method. Our research program aims to improve the cost-effectiveness of screening by developing a blood test to select patients for endoscopy/biopsy. Using our integrated lectin magnetic bead array (LeMBA) glycoprotein biomarker pipeline [1, 2] with Australian cohorts for the discovery and qualification phases, we identified serum lectin-glycoprotein biomarker candidates which can distinguish EAC from BE and healthy controls [3]. Here, we report the performance of these biomarker candidates in an independent patient cohort from the Ochsner Health System, New Orleans, USA. APPROACH & METHODOLOGY: Serum samples were collected from consenting patients undergoing endoscopy (Control - 16, BE - 13, and EAC - 10). The control group consisted of all patients not classified as BE with or without dysplasia, or EAC. LeMBA-MRM-MS was performed using 4 different lectins with different glycan specificities; AAL (Fucoseα1-2, -3, -6 linked glycan), EPHA (bisecting GlcNAc), JAC (Galα1-6GalNAc and Galβ1-3GalNAc), NPL (Manα1-6Man). Statistical analysis was performed using Shiny MixOmics as previously described [3]. RESULTS & DISCUSSION: Several lectin-protein candidate biomarkers cross-validated in the USA cohort. Most notably, differentially glycosylated complement component C9 is highly diagnostic in both cohorts, achieving area under the receiver operating curve (AUROC) of 0.74 (AAL-C9) to 0.90 (JAC-C9) as a single marker. Complement C9 binding to all four monitored lectins were increased 1.4 to 1.8 fold in EAC, compared to either BE or controls. Another consistent biomarker is gelsolin, with its binding to EPHA and NPL lectin significantly decreased in EAC, compared to either BE or controls. Hence, glycosylated C9 and gelsolin show promise as potential serum biomarkers for EAC screening, and will be further evaluated in prospective cohorts. REFERENCES: [1] Loo et al., J Proteome Res 9, 5496-5500 (2010); [2] Choi et al., Electrophoresis 32, 3564-3575 (2011); [3] Shah et al., Molecular & Cellular Proteomics 14:3023-39 (2015). Citation Format: Alok K. Shah, Virendra Joshi, Kim-Anh Le Cao, David C. Whiteman, Andrew P. Barbour, Michelle M. Hill. Towards a screening blood test for esophageal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4942.