Unknown,Transcriptomics,Genomics,Proteomics

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Progressive human proteinuric nephropathies

ABSTRACT: We obtained gene-expression profiles of microdissected renal-tubule cells from patients with proteinuric nephropathies. Based on the renal function during follow-up, the patients were divided in stable (n=14) and progressive (n=7) subjects (table 1). The cells of interest were laser-capture microdissected from frozen sections from archived kidney biopsy material. Initially all samples were processed as technical duplicates (2 x 21 arrays); due to a large number of signal-negative spots several arrays were excluded leaving 36 arrays for analysis. The samples P2, P6, P7, S10, S13 and S14 were analysed as individual arrays, all other samples were analysed after combination of duplicate arrays. Quality control: To test for reproducibility we calculated the intra-array variability of the duplicate arrays. Duplicate arrays were combined before statistical analysis where applicable. Patient and control characteristics can be found in the manuscript and on our website Frozen kidney biopsies were stained for alkaline phospatase, then the tubule cells were lasercapture microdissected using the PixCell II Laser Capture Microdissection System and CapSure; LCM Caps. Set of arrays that are part of repeated experiments Disease State: samples from patients with proteinuric nephropathy (stable or progressive) Biological Replicate Computed

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Rudnicki

PROVIDER: E-GEOD-11513 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Hypoxia response and VEGF-A expression in human proximal tubular epithelial cells in stable and progressive renal disease.

Rudnicki Michael M Perco Paul P Enrich Julia J Eder Susanne S Heininger Dorothea D Bernthaler Andreas A Wiesinger Martin M Sarközi Rita R Noppert Susie-Jane SJ Schramek Herbert H Mayer Bernd B Oberbauer Rainer R Mayer Gert G

Laboratory investigation; a journal of technical methods and pathology 20090112 3

Proteinuria, inflammation, chronic hypoxia, and rarefaction of peritubular capillaries contribute to the progression of renal disease by affecting proximal tubular epithelial cells (PTECs). To study the transcriptional response that separates patients with a stable course from those with a progressive course of disease, we isolated PTECs by laser capture microdissection from cryocut tissue sections of patients with proteinuric glomerulopathies (stable n=20, progressive n=11) with a median clinic ...[more]

PMID: 19139726

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Project description:These 95 arrays are the basis for Figure 2 of our manuscript "An interferon-response induced by tumor-stroma interaction in a subset of human breast cancers". Abstract:Background Communication between different cell types is a cardinal feature of multi-cellular organisms and perturbations in these cell-cell interactions are a key feature of cancer. However, little is known about the systematic effects of cell-cell interaction on global gene expression in cancer. Methods and Findings We used an ex vivo culture model to simulate tumor-stroma interaction by systematically co-cultivating breast cancer cells with stromal fibroblasts and determined associated gene expression changes with cDNA microarrays. The picture of heterotypic interaction effects that emerged from this analysis is complex, reflecting the variation in signaling capacities and responsiveness of the involved cells. A frequent and prominent response to epithelial-mesenchymal interaction was an induction of interferon-response genes, observed in 4 of the 7 breast cancer cell lines in response to co-culture with fibroblasts, but not in normal mammary epithelial cells. In response to close contact with these breast cancer cells, the fibroblasts secreted type I interferons, which, in turn, induced expression of the IRGs in the tumor cells. Immunohistochemical analysis of human breast cancer tissues showed that STAT1, the key transcriptional activator of the interferon-response genes, and itself an IRG, was expressed in a subset of the cancers, with a striking pattern of elevated expression in the cancer cells in contact with, or close proximity to, the tumor stroma ? paralleling the response seen in our ex vivo model. In vivo, expression of the interferon-response genes was remarkably coherent, providing a basis for segregation of the 295 early-stage breast cancers into two groups. Tumors with high expression levels (n=161) of IRG were associated with significantly shorter overall survival; 59 % at 10 years versus 80% for tumors with low interferon-response gene expression levels (n=134) (log-rank p=0.001). Conclusion Our results suggest that an interaction between some breast cancer cells and stromal fibroblasts can induce an interferon response, and that this response may be associated with a greater propensity for tumor progression. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed

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Progressive human proteinuric nephropathies

Publications

Hypoxia response and VEGF-A expression in human proximal tubular epithelial cells in stable and progressive renal disease.

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