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Identifying urinary RNA from biopsy associated urine as non-invasive biomarkers for kidney transplant patients

ABSTRACT: Identifying urinary RNA from biopsy associated urine as non-invasive biomarkers for kidney transplant patients

PROVIDER: PRJNA527211 | ENA |

REPOSITORIES: ENA

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Identifying urinary RNA from biopsy associated urine as non-invasive biomarkers for kidney transplant patients

Project description:To identify urinary RNA from biopsy associated urine as non-invasive biomarkers for kidney transplant patients

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Identifying urinary RNA from prospective urine as non-invasive biomarkers for kidney transplant patients

Project description:To identify urinary RNA from prospective urine as non-invasive biomarkers for kidney transplant patients

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Identifying urinary RNA from prospective urine as non-invasive biomarkers for kidney transplant patients

Project description:Identifying urinary RNA from prospective urine as non-invasive biomarkers for kidney transplant patients

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Differentially expressed genes and functional categories in biopsy, peripheral blood and urine from kidney transplant patients with acute and chronic rejection

Project description:Kidney transplantation is the treatment of choice for patients with end-stage chronic kidney disease (ESKD). Despite the usefulness of transplantation as replacement therapy, long-term graft survival represents a major challenge for transplant immunology. Although nowadays there has been an advance in understanding immunological mechanisms mediating rejection, and the improvement of immunomodulation therapies, there are still underlying molecular processes marking an important variability among patients, and presumably influencing allograft rejection. With our analysis we explored differences in gene expression by Next Generation Sequencing implementing RNA-Seq in biopsies, blood and urine from kidney transplant patients with acute and chronic rejection. For this, we performed an intra-outcome analysis simultaneously in acute and chronic rejection, with which we sought: 1. To identify differences in gene expression between peripheral blood vs renal tissue and peripheral blood vs urine in acute rejection and chronic rejection; 2. To identify the level of agreement in gene expression between renal tissue and urine in acute rejection and chronic rejection and 3. To identify genes and biological processes associated with acute rejection and chronic rejection that could be potentially detected in blood, and simultaneously in urine and biopsy in acute rejection and in chronic rejection.

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Specific normalization of urinary mRNAs reveals genome-wide patterns associated with renal allograft subclinical injury

Project description:urinary mRNA quantification using an Agilent 60k microarray in 26 stable kidney transplant patients with or without renal partial Epithelial to Mesenchymal Transition Subclinical pathological features on the 3-month biopsy of renal allografts predict a poor prognosis, but it is unclear whether surveillance biopsies are beneficial. Non-invasive biomarkers are wanted, and urinary pellet RNA quantification of selected candidate genes has been used with some success do detect overt rejection. We performed a mRNA microarray study using different normalization methods on the urinary cell pellet to evaluate the feasibility of using urine to detect renal partial epithelial mesenchymal transition of the renal allograft (renal pEMT) non-invasively in a group of 26 stable transplanted patients. We found that, when using a novel method of normalization by Upk1a mRNA, renal pEMT of the renal allograft was associated in urine with differential expression of genes belonging to predefined gene sets of kidney-expressed genes and epithelial mesenchymal transition genes. An unbiased pathway analysis revealed that the immune response was the main urinary biological process associated with pEMT in the kidney. In urine from patients with pristine biopsies, pEMT was not associated with inflammation, but with reduced metabolic functions. Thus, we show that pEMT translates into specific UPK1a-normalized mRNA patterns in urine and use genome-wide analyses to characterize underlying molecular patterns, i.e. increased inflammation and decreased metabolic functions.

2017-09-01 | GSE89652 | GEO

Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy

Project description:Background: Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30-1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as a simple and non-invasive liquid biopsy approach for measuring glioblastoma-associated biomarkers. Methods: Fifty urine specimens (15-60 ml) were collected from 24 catheterised glioblastoma patients immediately prior to primary (n=17) and recurrence (n=7) surgeries, following gross total resection (n=9), and from age/gender-matched healthy participants (n=14). EVs isolated by differential ultracentrifugation were characterised and extracted proteomes were analysed by high-resolution data-independent acquisition liquid chromatography tandem mass spectrometry (DIA-LC-MS/MS). Results: Overall, 6857 proteins were confidently identified in urinary-EVs (q-value≤0.01), including 94 EV marker proteins. Glioblastoma-specific proteomic signatures were determined, and putative urinary-EV biomarkers corresponding to tumour burden and recurrence were identified (FC≥|2|, adjust p-val≤0.05, AUC>0.9). Conclusion: In-depth DIA-LC-MS/MS characterisation of urinary-EVs substantiates urine as a viable source of glioblastoma biomarkers. The promising ‘liquid gold’ biomarker panels described here warrant further investigation.

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2020-02-20 | GSE112098 | GEO

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