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

Yusheng Lin, Hongmei Dong, Weilun Deng, Wan Lin, Kai Li, Xiao Xiong, Yi Guo, Fuyou Zhou, Changchun Ma, Yuping Chen, Hongzheng Ren, Haijun Yang, Ningtao Dai, Lang Ma, Stephen Meltzer, Sai Ching J. Yeung, Hao Zhang

Research output: Contribution to journalArticle

Abstract

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 (seG-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 seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-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. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n ¼ 220) and a validation cohort (n ¼ 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation. Conclusions: SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.

Original languageEnglish (US)
Pages (from-to)3035-3045
Number of pages11
JournalClinical Cancer Research
Volume25
Issue number10
DOIs
Publication statusPublished - Jan 1 2019

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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