Project description:Colorectal cancer is one of the most common cancers in the world. Histological staging is efficient but combination with molecular markers may improve tumors classification. Gene expression profiles have been defined as prognosis predictors among stage II and III tumors but their implementation in medical practice remains controversial. Stage-II tumors have been recognized as a heterogeneous group and high-risk morphologic features have been retained as justifying adjuvant chemotherapy. We propose here the investigation of clinical features and expression profiles from stage II and stage III colon carcinomas without DNA mismatch repair defect. A series of 130 colon cancer samples was retained. Expression profiles were established on oligonucleotide microarrays and processed in the R/Bioconductor environment. Hierarchical then supervised analyses were successively performed applying the data-sampling approach. A molecular signature of seven genes was found to cluster stage III tumors with an adjusted p-values lower than 10^-10. A subgroup of stage-II tumors aggregated this cluster in both series. No correlation was found between with the disease severity but the function of the discriminating genes suggests that tumors have been classified according to their putative response to adjuvant targeted or classic therapies. Further pharmacogenetic studies might document this observation. Expression profile of stage-II colon carcinomas distinguishes two patterns of tumors based on a 7-gene signature. One pattern is very similar to that of stage-III tumors and the corresponding tumors aggregate into a single cluster. Genes function suggests possible tumor determinism in drug response more than in prognosis evolution.
Project description:Transcriptome analysis of 130 breast cancer samples (41 TNBCÂ ; 30 Her2Â ; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines. This dataset contains 178 arrays. 153 arrays were used to analyze 130 unique breast cancer samples from as many patients and 23 technical duplicates. In addition 11 âNormalâ samples from healthy breast tissue obtained from mammoplasty are included, as well as a collection of 14 breast cancer cell lines. Data production involved different array batches and hybridation series which were accounted for in the pre-processing of the data.
Project description:Transcriptome analysis of 130 breast cancer samples (41 TNBCM-BM- ; 30 Her2M-BM- ; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines. This dataset contains 178 arrays. 153 arrays were used to analyze 130 unique breast cancer samples from as many patients and 23 technical duplicates. In addition 11 M-bM-^@M-^\NormalM-bM-^@M-^] samples from healthy breast tissue obtained from mammoplasty are included, as well as a collection of 14 breast cancer cell lines. Data production involved different array batches and hybridation series which were accounted for in the pre-processing of the data.
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 30 gastric cancer patients. Whole genomic CNAs in 30 human gastric cancers were analyzed using the Agilent aCGH-400K arrays. Matched normal tissues were used as the reference.
Project description:The goal of this project was to characterize DCs from lymphopenic mice, like RAG (recombination activated gene) deficient mice and to examine the influence of mature B and T cells on the antigen presenting ability of splenic cDCs. We demonstrate how cellular cross-talk can shape the character and function of cDCs. Lymphopenic conditions, where splenic cDCs have to develop and differentiate, drastically change their character and their ability to cross-present soluble antigen. In this approach we sorted out two populations (CD8?+ and CD8?-) of splenic dendritic cells (DCs) from untreated WT, and RAG2-/- C57Bl/6 mice. The age of mice was between 8-10 weeks. Further we isolated RNA and performed microarray analysis. Each DCs population was repeated twice.
Project description:Identification of a stable gene expression signature with high classifying potential to discriminate post-radiotherapy-induced thyroid tumors (follicular adenomas and papillary carcinomas) from their sporadic counterparts.
Project description:Type I Interferons encompasses a large family of closely related cytokines comprising of at least 13 IFN-α isotypes and single IFN-β. Both IFN-α and IFN-β exert their activity through a common receptor IFNAR. Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells. In this approach we sorted out two populations (CD8α+ and CD8α-) of splenic dendritic cells (DCs) from untreated WT, IFN-β-/- and IFNAR-/- C57Bl/6 mice. All mice were between 8-10 weeks old. Further we isolated RNA and performed microarray analysis. Each DCs population was repeated twice.
Project description:Proliferation, dedifferentiation, loss of cell-cell contacts and angiogenesis are among the first steps of the metastasis cascade. The complex molecular pathways associated with these events in canine mammary tumors are mostly unknown and the value of this spontaneous canine tumor as a comparative model for human breast cancer is therefore still under debate. Messenger RNA profiles of lymph-node positive canine mammary carcinomas and normal mammary glands of the same dogs were compared by microarray analysis to elucidate molecular pathways associated with metastatic progression. Differential gene expression was analyzed by gene set enrichment and pathway analysis and compared with the gene expression data of human breast cancer. Metastatic canine carcinomas had 1,312 significantly differentially expressed genes when compared to the corresponding normal mammary gland. This expression profile included a significantly increased expression of cell division and extracellular matrix invasion genes (MMP1, MMP11, MMP13, SERPINE1, TFPI2, TIMP3). In contrast, genes associated with epithelial differentiation (EGF, EGFR, KRT17, MAP2K6, STAT5), cell adhesion (CLDN5, CLDN8, CTNNAL1, MCAM, MUC1, PECAM1) and angiogenesis (ANGPT2, ANGPTL1, ANGPTL2, ANGPTL4, FGFR1, FIGF, TIE1) were mostly down-regulated. Interestingly, tumors had a significant decrease in membrane receptors and growth factor pathway gene expression (EGFR, FGFR1, GHR, LYVE1, PDGFR, PDGFR, TGFBR, TIE1), indicating a potential independence from these proliferative stimuli. Several of the identified deregulated pathways overlap with gene expression profiles of human breast cancer. Gene expression profiling of metastatic carcinomas therefore identified complex molecular pathways and functional gene families that are deregulated during malignant progression in the tumors. This study provides new insights into canine mammary tumor metastasis and suggests that canine mammary tumors may serve as a valuable model for the human disease. 13 simple mammary carcinomas with lymph node metastases at the time of tumor resection were compared with the non-neoplastic mammary gland of the same dogs. Sufficient amounts of normal mammary gland were not available for dogs no. 1 (822) and 9 (61). In addition, one normal sample without matching tumor sample was analyzed (no. 8; 2609). All patients had no radiographically detectable pulmonary metastases at the time of tumor resection. Postoperative survival was analyzed by bi-yearly telephone interviews with the owners or the attending veterinarian. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases (nos. 1-7, 9-12) or necropsy (nos. 13 and 14). Necropsy was not authorized by the owners of dogs nos. 1-7 and 9-12. Tissue specimens of tumors and lymph node metastases were fixed in neutral-buffered 4% formalin or snap frozen in liquid nitrogen within 15 minutes after resection and stored at -80ºC until further use. Formalin-fixed tumor tissue samples were routinely embedded in paraffin and sections of 2-μm thickness were mounted on adhesive glass slides and stained with hematoxylin and eosin. Tumors and lymph nodes were evaluated histologically independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors (Misdorp et al. 1999).
Project description:We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences. Gene expression profiles were used to identify unique immunobiologic sub-types of posterior fossa pediatric ependymoma. Gene expression profiles were generated from surgical tumor (ependymoma) (n=65) using Affymetrix HG-U133plus2 chips (Platform GPL570). Normalization was performed on our entire cohort of ependymoma. Of the 65 samples, a sub-set of 58 were used in the corresponding manuscript. Excluded samples are noted. Gene expression profiles were filtered to obtain gene expression of key immune cell markers. Comparative analyses between tumor samples were used to identifiy unique immunobiology between posterior fossa sub-groups.