Evaluation of plasma exosomal miR-214-3p as a potential biomarker for diagnosis and prognosis of uveal melanoma
Zhou Wenda, Shao Lei, Dong Li, Shi Xuhan, Zhang Ruiheng, Li Heyan, Wu Haotian, Wei Wenbin
Abstract
ObjectiveTo investigate the differential expression of microRNA (miR)-214-3p in plasma exosomes in different types of uveal melanoma (UM) and evaluate whether miR-214-3p is a potential molecular biomarker for the diagnosis and prognosis of UM.
MethodsTwenty-five UM in situ patients who received the enucleation of eyeball were enrolled at Beijing Tongren Hospital from December 2015 to October 2019, including 10 with epithelioid cell melanoma and 10 with spindle cell melanoma as well as 5 metastatic UM patients (1 with spindle cell-like melanoma and 4 with epithelioid cell-like melanoma) and 10 healthy subjects were enrolled during the same period.Blood sample was collected from all the subjects for the isolation of plasma exosomes.The morphology of exosomes was examined under the electron microscope.The exsomal marker proteins were identified by Western blot.The expression level of miR-214-3p in plasma exosomes was detected by real-time fluorescence quantitative PCR.The differential expression of miR-214-3p among different types of UM patients and healthy controls was compared.The diagnostic and classification performance of exosomal miR-214-3p was evaluated using receiver operating characteristic curve.Written informed consent was obtained from each subject prior to entering the study cohort.This study protocol was approved by an Ethics Committee of Capital Medical Univeristy (No.TRECKY2018-056).
ResultsThe isolated exosomes were hemispherical in shape with a concavity on one side.The diameter of the exosomes was about 100 nm and the particle diameter of vesicles from samples was (82.0±2.7) nm.TSG101 protein was detectable and Calnexin protein was not found in the exosomes.The relative expression levels of plasma exosomal miR-214-3p in healthy control group, in situ UM group and metastatic UM group were 0.86(0.57, 1.49), 0.24(0.10, 0.67), and 0.43(0.23, 0.56), respectively.The miR-214-3p relative expression level in plasma exosomes of in situ UM patients and metastatic UM patients was significantly lower than that of healthy controls, and the differences were statistically significant (Z=2.62, P<0.01; Z=2.08, P<0.05). The relative expression levels of exosomal miR-214-3p in spindle cell-like UM group and epithelioid cell-like UM group were 0.11(0.07, 0.64) and 0.46(0.14, 0.91), respectively, and no significant difference was found in the expression level of plasma exosomal miR-214-3p among different types of UM (all at P>0.05). The area under the curve of plasma exosomal miR-214-3p for UM diagnosis was 0.795.
ConclusionsPlasma exosomal miR-214-3p level is significantly reduced in both in situ UM patients and metastatic UM patients.Plasma exosomal miR-214-3p is a new potential diagnostic biomarker for UM, but the exosomal miR-214-3p appears to not be able to distinguish the types of UM.
Key words:
Uveal melanoma; Circulating microRNA; Biomarkers; Exosomes; Early diagnosis; Prognostic evaluation
Contributor Information
Zhou Wenda
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Shao Lei
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Dong Li
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Shi Xuhan
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Zhang Ruiheng
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Li Heyan
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Wu Haotian
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Wei Wenbin
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophtahlmology &
Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
