Identification and validation of circulating exosomes‐based liquid biopsy for esophageal cancer

BACKGROUND: Early detection of esophageal squamous cell carcinoma (ESCC) recurrence is a key element for follow‐up care and surveillance. The aim of this study is to detect the level of circulating exosomes (CEs) in ESCC patient and clarify its clinical significance. METHODS: In this study, 200 serum samples of ESCC patients were obtained from the Zhejiang Cancer Hospital Biospecimen Repository. Total CEs were purified by selectively capturing epithelial cell adhesion molecule positive exosomes, using magnetic‐bead technique. enzyme‐linked immunosorbent assay (ELISA) was performed to measure the concentration level of CEs. The oncogenic potential of CEs was analyzed in vitro. RESULTS: Serum concentration of CEs was significantly higher in ESCC patients than in healthy controls (P < 0.01). Receiver‐operating characteristic curve analysis demonstrated that CEs concentration could distinguish patients with ESCC from healthy individuals with a sensitivity of 75% and a specificity of 85%. Kaplan‐Meier analysis demonstrated that the increased CEs concentration was associated with poor overall survival (P = 0.01) and progression free survival (P = 0.03) in ESCC patients. Multivariate cox regression analysis revealed that CEs concentration was an independent prognostic marker for overall survival in ESCC patients (P < 0.01). Results from transwell and wound scratching experiments showed that the CEs could promote cell migration and invasion. CONCLUSIONS: This study clearly demonstrates that CEs from ESCC patients are stable enough to be measured and their levels in ESCC patients are significantly upregulated. Circulating exosomes could serve as a novel noninvasive biomarker for detection of ESCC. Their involvement in carcinogenesis must be further established.