Project description:Both cigarette smoking and obesity have been implicated in increased risk of clear cell renal cell carcinoma (ccRCC); however, there are limited data regarding the molecular mechanisms that underlie these associations. We used a multi-stage design to identify and validate specific molecular targets that are associated with smoking or obesity-related ccRCC.
Project description:Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. To better understand the biology of this tumor, we analyze the miRNA expression profiles of a set of CCPRCC by microarrays.
Project description:Both cigarette smoking and obesity have been implicated in increased risk of clear cell renal cell carcinoma (ccRCC); however, there are limited data regarding the molecular mechanisms that underlie these associations. We used a multi-stage design to identify and validate specific molecular targets that are associated with smoking or obesity-related ccRCC. The data deposited herein are comprised of two batches of samples that were processed at two different time periods (please see Supplementary Data in Eckel-Passow et al. Carcinogenesis first published online December 28, 2013; doi:10.1093/carcin/bgt485). The first batch of samples consisted of 12 obese subjects and 13 non-obese subjects; all of whom were self-reported never-smokers. Each of the 12 obese subjects had microarray data available on both the patient-matched tumor and adjacent-normal tissues. All of the 13 non-obese subjects had microarray data available on the tumor tissue; however, only 9 of these 13 also had microarray data available on the patient-matched adjacent-normal tissue. The second batch of samples consisted of 16 self-reported smokers and 19 self-reported never smokers; all of whom were non-obese. This second batch of samples also contained 7 subjects who were obese and self-reported smokers. All subjects in the second batch had microarray data available on both the patient-matched tumor and adjacent-normal tissues. Lastly, two of the 13 patients in batch 1 were replicated in batch 2; both were non-obese and a non-smoker. These two technical replicates (two tumor samples and two normal samples) were included during normalization but removed prior to analysis. The cel files are Par007U133Plus2.0.CEL Par008U133Plus2.0.CEL Par041U133Plus2.0.CEL Par042U133Plus2.0.CEL The metadata "duplicate" column can also be used to exclude these samples. This dataset is part of the TransQST collection.
Project description:We performed a transcriptomic analysis in a cohort of 6 Collecting Duct Carcinoma, 5 Clear Cell Renal Cell Carcinoma and 4 non-matched normal renal tissues to unravel the underlying biological and molecular determinants and to identifiy specific genes and pathways of this rare tumor type.
Project description:The ubiquitin proteasome system governs a wide spectrum of cellular events and offers therapeutic opportunities for pharmacological intervention in cancer treatment. Renal clear cell carcinoma represents the predominant histological subtype and accounts for the majority of cancer death related to kidney malignancies. Through a systematic survey in the association of human ubiquitin-specific proteases with patient prognosis of renal clear cell carcinoma and subsequent phenotypic validation, we uncovered the tumor-promoting role of USP35. Biochemical characterizations confirmed the stabilizing effects of USP35 towards multiple members of the IAP family in an enzymatic activity-dependent manner. USP35 silencing led to reduced expression levels of IAP proteins, which were accompanied with increased cellular apoptosis. Further transcriptomic analysis revealed that USP35 knockdown altered expression levels of NRF2 downstream transcripts, which were conferred by compromised NRF2 abundance. USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction. Finally, induced USP35 knockdown markedly attenuated xenograft formation of renal clear cell carcinoma in nude mice. Hence, our findings identify a number of USP35 substrates and reveal the protecting role of USP35 against both apoptosis and ferroptosis in renal clear cell carcinoma.
Project description:In order to clarify the molecular mechanism involved in renal carcinogenesis, and identify molecular targets for diagnosis and treatment, we analyzed genome-wide gene expression profiles of 15 surgical specimens of clear cell renal cell carcinoma (RCC), compared to normal renal cortex, using a combination of laser microbeam microdissection (LMM) with a cDNA microarray representing 27,648 genes.
Project description:We performed a genome-wide assessment of copy number alterations and LOH regions in a collection of clear cell renal carcinoma tissue samples as compared to matched normal blood samples. Affymetrix GeneChip Human Mapping 100K SNP arrays were used. This experiment includes GeneChip Human Mapping 50K Xba array files.
