TY - JOUR
T1 - Evaluation of salivary exosomal chimeric GOLM1-NAA35 RNA as a potential biomarker in esophageal carcinoma
AU - Lin, Yusheng
AU - Dong, Hongmei
AU - Deng, Weilun
AU - Lin, Wan
AU - Li, Kai
AU - Xiong, Xiao
AU - Guo, Yi
AU - Zhou, Fuyou
AU - Ma, Changchun
AU - Chen, Yuping
AU - Ren, Hongzheng
AU - Yang, Haijun
AU - Dai, Ningtao
AU - Ma, Lang
AU - Meltzer, Stephen J.
AU - Yeung, Sai Ching J.
AU - Zhang, Hao
N1 - Funding Information:
S.J. Meltzer is a consultant/advisory board member for TwoXAR, Inc. S.-C.J. Yeung is a consultant/advisory board member for Celgene, and reports receiving commercial research grants from DepMed and Bristol-Myers Squibb ARISTA. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85065781722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065781722&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-3169
DO - 10.1158/1078-0432.CCR-18-3169
M3 - Article
C2 - 30745298
AN - SCOPUS:85065781722
SN - 1078-0432
VL - 25
SP - 3035
EP - 3045
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -