Multiplex SERS-Lectin-Immunoassay for Esophageal Adenocarcinoma Screening

Endoscopy and tissue biopsy are the gold standard methodology of diagnosing esophageal adenocarcinoma (OAC) and its premalignant condition, Barrett's esophagus (BO). This procedure is invasive and unsuitable for population screening, leading to late diagnosis and poor prognosis of most OAC. In this context, identifying the likelihood of OAC and/or BO with a pre-endoscopic population-based screening test utilizing liquid biopsies would be an ideal method to stratify patients for endoscopy. Herein, we develop a surface-enhanced Raman scattering lectin-immunoassay (SERS-LIA) to accurately measure serum jacalin (JAC) lectin-binding complement C9 (JAC-C9), JAC-gelsolin (JAC-GSN), and JAC-prekallikrein (JAC-KLKB1). Multiplexing via plasmonic nanoparticles enables sensitive serum detection of 30 ng mL(-1) for JAC-C9, 53 ng mL(-1) for JAC-GSN, and 23 ng mL(-1) for JAC-KLKB1. The diagnostic performance of SERS-LIA was evaluated on 42 serum samples (15 healthy controls, 16 BO, and 11 OAC). Multilinear regression analysis (MLR) achieved excellent receiver operating characteristic (ROC) curves with an area under the curve of 1.00 for OAC versus BO, 1.00 for OAC versus healthy, and 0.98 for OAC versus BO. These findings suggest that our developed multiplex SERS-LIA could be a promising liquid biopsy platform for OAC screening.