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

• Published in: Molecular cancer Vol. 21; no. 1; pp. 21 - 13
• Main Authors: Li, Kai, Lin, Yusheng, Luo, Yichen, Xiong, Xiao, Wang, Lu, Durante, Kameron, Li, Junkuo, Zhou, Fuyou, Guo, Yi, Chen, Shaobin, Chen, Yuping, Zhang, Dianzheng, Yeung, Sai-Ching Jim, Zhang, Hao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.01.2022; BioMed Central; BMC
• Subjects: Biomarkers; Biomarkers, Tumor; Biopsy; Cancer therapies; Combined Modality Therapy; Development and progression; Diagnosis; Disease Management; Endoscopy; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - etiology; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - therapy; Esophagus; Exosomes; Exosomes - metabolism; Female; Gene Expression Profiling; Hospitals; Humans; Hypoxia; Liquid-biopsy signature; Male; Metastasis; Neoplasm Grading; Neoplasm Staging; Nuclease; Pre-operative biomarker of adjuvant therapy; Prognosis; Prospective Studies; RNA sequencing; RNA, Small Untranslated - genetics; RNA, Small Untranslated - metabolism; Saliva; Saliva - metabolism; Sample size; Sensitivity and Specificity; Sequencing of salivary extracellular vesicles; Squamous cell carcinoma; Transfer RNA; Transfer RNA-derived small RNA; tRNA; tRNA-derived fragments; China; Esophageal carcinoma; Liquid-biopsy signature; Transfer RNA-derived small RNA; Pre-operative biomarker of adjuvant therapy; Sequencing of salivary extracellular vesicles; tRNA-derived fragments
• DOI: 10.1186/s12943-022-01499-8
• ISSN: 1476-4598

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