Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human vulvar epithelial neoplasia vs normal controls

ABSTRACT: In order to understand the molecular mechanism behind Vulvar Intraepithelial Neoplasia (VIN), we have analyzed the gene expression profile of VIN lesions in comparison to controls. Experiment Overall Design: Nine VIN and 10 control samples were collected. RNA of each sample was isolated and analyzed using Affymetrix Human U133plus2 GeneChips.

ORGANISM(S): Homo sapiens

SUBMITTER: Lindy Santegoets

PROVIDER: E-GEOD-5563 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.

Santegoets Lindy A M LA Seters Manon van Mv Helmerhorst Theo J M TJ Heijmans-Antonissen Claudia C Hanifi-Moghaddam Payman P Ewing Patricia C PC van Ijcken Wilfred F J WF van der Spek Peter J PJ van der Meijden Willem I WI Blok Leen J LJ

International journal of cancer 20070801 4

<h4>Unlabelled</h4>Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). ...[more]

PMID: 17471573

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Project description:Polyoma virus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. Microscopic descriptions of PVAN are very similar to T-cell mediated rejection (TCMR) and have unclear underlying molecular mechanisms. To identify PVAN-specific gene expression, we analyzed 162 kidney biopsies with and without PVAN for global gene expression. Unsupervised hierarchical clustering analysis of all 162 biopsies revealed high similarity between PVAN and TCMR gene expression. Increasing the stringency for the specificity (p <0.001 and >2-fold expression) between PVAN and TCMR, 158 and 252 unique PVAN and TCMR injury-specific probesets were observed, respectively. While TCMR-specific probeset were overwhelmingly involved in immune response costimulation (CTLA4, CD28, CD86) and TCR (NFATC2, LCP2) signaling, PVAN-specific probesets were mainly related to viral replication process (IFITM1, LTF, NOSIP, RARRES3), RNA polymerase assembly (POLR2l, TAF10, RPS15) and pathogen recognition receptors (C1QA, C3, CFD). A principal component analysis using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific probesets (RPS15, CFD, LTF, and NOSIP) by QPCR and further confirmation by IHC of 2 PVAN-specific proteins with anti-viral function (LTF and IFITM1) was done, showing significantly higher expression within interstitial cellular infiltrates and in tubuli in PVAN specimens as compared to TCMR and NL kidney biopsies. In conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, particular PVAN-specific transcripts were identified with well-known anti-viral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design. A total of 168 kidney biopsies from kidney transplant patients were used. The kidney biopsies included renal biopsies from PVAN (n=10), T cell mediated cellular rejection (n=26), patients with IFTA (n=59), patients with stable grafts (STA) (n=73). This dataset is part of the TransQST collection.

Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage. We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection.

Project description:Background: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1Î±,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown. Results: We examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n=4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60 % up), 48 h, 3566 (38 % up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways). There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h. Conclusions: Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis. Experiment Overall Design: RWPE1 cells were treated with medium containing 100 nM of 1,25(OH)2D or vehicle (0.1% ethanol) for 6, 24 or 48 hours (n=4 per treatment, 24 total samples). The transcripts levels in each sample were measured by using the Affymetrix HU133 plus 2.0 GeneChip (Affymetrix, Santa Clara, CA).

Dataset Information

Transcription profiling of human vulvar epithelial neoplasia vs normal controls

Publications

HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.

Similar Datasets

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