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Gene array analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue

ABSTRACT: Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53757 | GEO | 2014/01/03

SECONDARY ACCESSION(S): PRJNA232816

REPOSITORIES: GEO

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Gene array analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue

Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy. Patient tissue samples were sorted into disease stages based on pathology reports. RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.

2014-01-03 | E-GEOD-53757 | biostudies-arrayexpress

Proteomic analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue

Project description:We analyzed 84 tumor/normal pairs (177 total) using standard shotgun proteomic techniques in order to characterize the molecular landscape of clear cell renal cell carcinoma (ccRCC) and interrogated changes in protein abundance and biological pathways with ccRCC grade. These tissues were distributed across stage 1 (n = 34), 2 (n = 40), 3 (n = 42), and 4 (n = 52), with 9 pairs also including samples from metastasized tumor. These data can be (and were) combined with a previously published transcriptomic data set from the same sample cohort (NCBI GEO: GSE53757).

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Gene array analysis of anaplastic thyroid carcinoma tissue versus matched and unmatched normal thyroid tissue

Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples. RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.

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Epigenome analysis of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue

Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues.

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Gene array analysis of anaplastic thyroid carcinoma tissue versus matched and unmatched normal thyroid tissue

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Epigenome analysis of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue

Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. TheÂ IlluminaÂ Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximatelyÂ 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues. Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip v1.2

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Proteomic analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue

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Identification of DNA methylation-independent epigenetic events underlying clear cell renal cell carcinoma

Project description:Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome, and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared to commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Examination of 3 different histone modifications in 2 patient tumor and adjacent normal samples.

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Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma

Project description:Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.

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Quantitative proteomics identifies secreted diagnostic biomarkers as well as tumor-dependent prognostic targets for clear cell Renal Cell Carcinoma

Project description:Clear cell Renal Cell Carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified 4 putatively secreted biomarker candidates, namely PLOD2, FERMT3, SPARC and SIRPα, as highly expressed proteins that are not affected by intra- and inter-tumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of ccRCC patients, making it a promising marker for clinical screening assays. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared to cluster 2 tumors. Moreover, among the most significant clustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC.

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