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-NchiRNA) in esophageal squamous cell carcinoma (ESCC).
EXPERIMENTAL DESIGN
In a retrospective study, the prognostic significance of
G-NchiRNA was determined in ESCC tissues. The correlation between se
G-NchiRNA and circulating exosomal or tumoral
G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, se
G-NchiRNA 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-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. Se
G-NchiRNA levels reflected tumor burden
in vivo and correlated with tumor
G-NchiRNA levels. In prospective studies of a training cohort (
n = 220) and a validation cohort (
n = 102), se
G-NchiRNA levels were substantially reduced after ESCC resection. Moreover, se
G-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in se
G-NchiRNA levels also predicted PFS of patients after chemoradiation.
CONCLUSIONS
Se
G-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.