Evaluation of salivary exosomal chimeric GOLM1-NAA35 RNA as a potential biomarker in esophageal carcinoma

Purpose: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (se G-N chiRNA) in esophageal squamous cell carcinoma (ESCC). Experimental Design: In a retrospective study, the prognostic significance of G-N chiRNA was determined in ESCC tissues. The correlation between se G-N chiRNA and circulating exosomal or tumoral G-N chiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, se G-N chiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS). Results: Exosomal G-N chiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. Se G-N chiRNA levels reflected tumor burden in vivo and correlated with tumor G-N chiRNA levels. In prospective studies of a training cohort ( n = 220) and a validation cohort ( n = 102), se G-N chiRNA levels were substantially reduced after ESCC resection. Moreover, se G-N chiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in se G-N chiRNA levels also predicted PFS of patients after chemoradiation. Conclusions: Se G-N chiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.