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A circulating exosomal microRNA panel as a novel biomarker for monitoring post-transplant renal graft function.

ABSTRACT: Accurate and effective biomarkers for continuous monitoring of graft function are needed after kidney transplantation. The aim of this study was to establish a circulating exosomal miRNA panel as non-invasive biomarker for kidney transplant recipients. Plasma exosomes of 58 kidney transplant recipients and 27 healthy controls were extracted by gel exclusion chromatography and characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blotting. Post-transplant renal graft function was evaluated by estimated glomerular filtration rate (eGFR). Quantitative real-time polymerase chain reaction was used to determine the expression of exosomal microRNAs (miRNAs). Exosomal miR-21, miR-210 and miR-4639 showed negative correlations with eGFR in the training set and were selected for further analysis. In the validation set, miR-21, miR-210 and miR-4639 showed the capability to discriminate between subjects with chronic allograft dysfunction (eGFR < 60 mL/min/1.73 m2 ) and those with normal graft function (eGFR > 90 mL/min/1.73 m2 ). Three-miRNA panel exhibited higher accuracy compared with individual miRNAs or double indicators. One-year follow-up revealed a stable recovery of allograft function in subjects with low calculated score from three-miRNA panel (below the optimal cut-off value). In conclusion, a unique circulating exosomal miRNA panel was identified as an effective biomarker for monitoring post-transplant renal graft function in this study.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7579686 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A circulating exosomal microRNA panel as a novel biomarker for monitoring post-transplant renal graft function.

Chen Yimeng Y Han Xu X Sun Yangyang Y He Xiaozhou X Xue Dong D

Journal of cellular and molecular medicine 20200911 20

Accurate and effective biomarkers for continuous monitoring of graft function are needed after kidney transplantation. The aim of this study was to establish a circulating exosomal miRNA panel as non-invasive biomarker for kidney transplant recipients. Plasma exosomes of 58 kidney transplant recipients and 27 healthy controls were extracted by gel exclusion chromatography and characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blotting. Post-transplant r ...[more]

PMID: 32918330

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Project description:BackgroundSmall cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis.MethodsTo investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs.ResultsFrom the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers.ConclusionOur study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

Dataset Information

A circulating exosomal microRNA panel as a novel biomarker for monitoring post-transplant renal graft function.

Publications

A circulating exosomal microRNA panel as a novel biomarker for monitoring post-transplant renal graft function.

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