Evaluation of Salivary Exosomal Chimeric <i>GOLM1-NAA35</i> RNA as a Potential Biomarker in Esophageal Carcinoma.

Abstract

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 <i>GOLM1-NAA35</i> chimeric RNA (se<i>G-N</i>chiRNA) in esophageal squamous cell carcinoma (ESCC). In a retrospective study, the prognostic significance of <i>G-N</i>chiRNA was determined in ESCC tissues. The correlation between se<i>G-N</i>chiRNA and circulating exosomal or tumoral <i>G-N</i>chiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, se<i>G-N</i>chiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS). Exosomal <i>G-N</i>chiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. Se<i>G-N</i>chiRNA levels reflected tumor burden <i>in vivo</i> and correlated with tumor <i>G-N</i>chiRNA levels. In prospective studies of a training cohort (<i>n</i> = 220) and a validation cohort (<i>n</i> = 102), se<i>G-N</i>chiRNA levels were substantially reduced after ESCC resection. Moreover, se<i>G-N</i>chiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in se<i>G-N</i>chiRNA levels also predicted PFS of patients after chemoradiation. Se<i>G-N</i>chiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.