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Clin Cancer Res. 2019 May 15;25(10):3035-3045. doi: 10.1158/1078-0432.CCR-18-3169. Epub 2019 Feb 11.

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

Lin Y1,2,3, Dong H1,3,4, Deng W3, Lin W3, Li K3, Xiong X3, Guo Y5, Zhou F6, Ma C7, Chen Y8, Ren H3, Yang H9, Dai N9, Ma L10, Meltzer SJ11, Yeung SJ12,13, Zhang H14,2,3,4.

Author information

1
Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China.
2
Department of Immunotherapy and Gastrointestinal Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
3
Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.
4
Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong, China.
5
Endoscopy Center, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
6
Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan, China.
7
Department of Radiation Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
8
Department of Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
9
Department of Pathology, Anyang Tumor Hospital, Anyang, Henan, China.
10
Department of Gastroenterology, University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
12
Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
13
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas.
14
Institute of Precision Cancer Medicine and Pathology, Jinan University Medical College, Guangzhou, Guangdong, China. haozhang@jnu.edu.cn.

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 = 220) and a validation cohort (n = 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.

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