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 chimeric RNA (sechiRNA) in esophageal squamous cell carcinoma (ESCC).
Experimental Design: In a retrospective study, the prognostic significance of chiRNA was determined in ESCC tissues. The correlation between sechiRNA and circulating exosomal or tumoral chiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, sechiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).
Results: Exosomal chiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SechiRNA levels reflected tumor burden and correlated with tumor chiRNA levels. In prospective studies of a training cohort ( = 220) and a validation cohort ( = 102), sechiRNA levels were substantially reduced after ESCC resection. Moreover, sechiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in sechiRNA levels also predicted PFS of patients after chemoradiation.
Conclusions: SechiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.
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| http://dx.doi.org/10.1158/1078-0432.CCR-18-3169 | DOI Listing |
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