A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study.

Abstract

BACKGROUND:

The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC).

METHODS:

Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature.

RESULTS:

The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90-8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24-6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29-0.77) and PFS (HR 0.36, 95%CI 0.21-0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort.

CONCLUSIONS:

The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy.

TRIAL REGISTRATION:

A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507 . Registered 3 April 2016 - Retrospectively registered.

• Authors: Kai Li, Yusheng Lin, Yichen Luo, Xiao Xiong, Lu Wang, Kameron Durante, Junkuo Li, Fuyou Zhou, Yi Guo, Shaobin Chen, Yuping Chen, Dianzheng Zhang, Sai-Ching Jim Yeung, Hao Zhang
• Journal: Molecular cancer (Mol Cancer) Vol. 21 Issue 1 Pg. 21 (01 18 2022) ISSN: 1476-4598 [Electronic] England
• PMID: 35042519 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Biomarkers, Tumor
• RNA, Small Untranslated

Topics

• Biomarkers, Tumor
• Combined Modality Therapy
• Disease Management
• Esophageal Neoplasms (diagnosis, etiology, metabolism, therapy)
• Exosomes (metabolism)
• Female
• Gene Expression Profiling
• Humans
• Male
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Prospective Studies
• RNA, Small Untranslated (genetics, metabolism)
• Saliva (metabolism)
• Sensitivity and Specificity