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Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas

ABSTRACT: Presented is the differential expression of mRNA and miRNA in 44 Stage I and Stage II patients who developed metastasis within 5 years of nephrectomy, compared to 21 patients who remained disease free. Extracted RNA from nephrectomy specimens preserved in FFPE blocks was sequenced using RNAseq. MiRNA expression was done using the TaqMan OpenArray qPCR protocol.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143630 | GEO | 2020/07/27

REPOSITORIES: GEO

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Prognostic Molecular Biomarkers for Metastatic Progression in Stage I and II Clear Cell Renal Cell Carcinomas

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Project description:MicroRNAs (miRNAs) are short single stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. Because of the lack of corresponding data in clear renal cell carcinoma (ccRCC) we have performed genome-wide expression profiling of miRNAs using microarray analysis and quantification of specific miRNAs by TaqMan real-time RT-PCR. Matched malignant and non-malignant tissue samples from two independent 12 ccRCC sets were profiled. The microassay-based experiments identified 14 overexpressed and 20 downregultaed miRNAs in malignant samples. Expression in ccRCC tissue samples compared to matched non-malignant samples measured by RT-PCR was increased by 2.7 to 28fold for the hsa-mir-16, -452, -224, -155, and -210, but decreased by 6.2 to 96fold for hsa-mir-200b, -363, , -429, -200c, -514, and -141. No significant associations between these differentially expressed miRNAs and the clinico-pathological factors tumor stage, grade, and survival rate were found. Nevertheless, malignant and non-malignant tissue could clearly be differentiated by their miRNA profile . A combination of miR-141 and miR-155 resulted in a 96% overall correct classification of samples. The presented differential miRNA pattern provides a solid basis for further validation including functional studies. The study was performed with two independent sample sets. For each set 12 kidney tissue sample pairs were derived from adult patients undergoing radical nephrectomy at the University Hospital CharitÃ©. All tumor types were clear renal cell carcinoma. Tumor classification and stage were established according to the 2002 TNM System and the 2004 WHO Classification. Matched malignant (#NC (e.g. 2NC)) and non-malignant (#NN (e.g. 1NN)) tissue samples from two independent 12 ccRCC sets were profiled.

2010-06-25 | E-GEOD-12105 | biostudies-arrayexpress

Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas.

Project description: Not available

| S-EPMC7431518 | biostudies-literature

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Project description:Murine lung miRNAs were profiled by rodent TaqMan OpenArray after flaxseed feeding and/or radiation exposure

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Deregulated Expression of the 14q32 miRNA Cluster in Clear Cell Renal Cell Carcinomas

Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.

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