Abstract

To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs). EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis. miRNA expression was examined by quantitative reverse transcription-polymerase chain reaction. Lastly, proteomic analysis of RCC cells transfected with a miRNA inhibitor was performed to identify its potential targets. Microarray analysis revealed that nine miRNAs were increased by more than 1.5-fold in EVs from patients with RCC. Among them, miRNA-4525 was significantly elevated; miRNA-4525 expression was higher in RCC tissue than in the adjacent normal tissue. Proteomic analysis identified alpha fetoprotein and albumin as its potential targets. These findings suggest the potential of miRNA-4525 in serum EVs as a novel biomarker for advanced RCC.

Highlights

  • Recent advances in cancer research have provided new options to treat advanced and metastatic renal cell carcinoma

  • Nine were found to be up-regulated by more than 1.5-fold in extracellular vesicles (EVs) isolated from patients with either localized or advanced renal cell carcinoma (RCC) compared with controls (Table II)

  • In order to obtain miRNA profiling data of serum EVs with minimal contamination of serum protein-bound miRNAs, we performed microarray analysis of EVs isolated by TIM4-conjugated beads, resulting in detection of more than 1,700 miRNAs

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Summary

Objectives

To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs)

Methods
Results
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