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Urinary exosomal long noncoding RNAs may be novel biomarkers for the diagnosis of clear cell renal cell carcinoma

ABSTRACT: Background: Renal cell carcinoma, which presents no significant clinical manifestations at early stages, is one of the few tumors with an increasing worldwide incidence. This malignancy cannot be directly detected by tumor markers in body fluid without information from imaging examinations. Approximately 30–40% of patients with kidney cancer exhibit distant metastasis at diagnosis, and their 5-year survival rate is much lower than that of patients with early-stage renal cell carcinoma. Thus, the early diagnosis of renal cell carcinoma is extremely important. The aim of this study was to investigate the utility of urinary exosomal long noncoding RNA (lncRNA) as a new potential diagnostic marker for renal cell carcinoma. Methods: Exosomes were isolated by ultracentrifugation from 50-ml urine samples from 10 patients with clear cell renal cell carcinoma and 10 matched healthy donors. Differentially expressed lncRNAs were analyzed by next-generation sequencing and further validated in kidney cancer cell lines, tissues and urinary exosomes. Then, we evaluated the sensitivity, specificity, clinical diagnostic value and stability of the selected lncRNAs. Results: The levels of lncRNAs NR_040448 and NR_033390 in urinary exosomes can likely indicate the presence of renal cell carcinoma. In addition, RNA protected by exosomes was stable enough to serve as a biomarker. Conclusion: Urinary exosomal lncRNA is a promising marker for the early diagnosis of renal cell carcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125442 | GEO | 2019/01/23

REPOSITORIES: GEO

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Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.

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Urinary exosomal long noncoding RNAs may be novel biomarkers for the diagnosis of clear cell renal cell carcinoma

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