ABSTRACT: Gene Expression data from Pdx-1CreAPC+/LP53L/L pancreatic ductal adenocarcinoma (PDAC) cells versus Pdx-1CreP53L/L normal pancreatic ductal cells
Project description:To further development of our lncRNA and mRNA expression approach to pancreatic ductal adenocarcinoma(PDAC), we have employed lncRNA and mRNA microarray expression profiling as a discovery platform to identify lncRNA and mRNA expression in pancreatic ductal adenocarcinoma.Human pancreatic ductal adenocarcinoma tissues and normal pancreatic tissues from PDAC donors and other duodenum diseases donors. analyze mRNA and lncRNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The variable 'MultiOmicsClassification' indicates the resulting sample's group. 'CIMPclass' is the CpG island methylator phenotype as estimated from the methylation arrays analysis. In this dataset, Illumina Infinium HumanCode-24 BeadChips SNP arrays were used to analyze the DNA xenografts samples from pancreatic ductal adenocarcinoma.
Project description:To explore the potential involvement of circular RNAs (circRNAs) in pancreatic ductal adenocarcinoma (PDAC) oncogenesis, we conducted circRNA profiling in six pairs of human PDAC and adjacent normal tissue by microarray. Our results showed that clusters of circRNAs were aberrantly expressed in PDAC compared with normal samples, and provided potential targets for future treatment of PDAC and novel insights into PDAC biology. Analyze circular RNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform.
Project description:We generated novel patient derived xenograft (PDX) and cell line -derived xenograft models for pancreatic ductal adenocarcinoma (PDAC) which reflect different molecular subtypes. Pancreatic ductal adenocarcinoma is currently the tumor with the fourth highest mortality rate. Recently, subtypes of PDAC have been reported by Collisson et al (Nat. Med. 17(4) 2011. DOI: 10.1038/nm.2344). However current fetal calf serum (FCS) cultured cell lines do not accurately model these subtypes. We thus generated novel serum-free cell lines derived from primary patient xenografts. We here analyse the gene-expression profiles of the xenografts and the derived cell lines. We show that indeed three different subtypes can be separated in our models based on gene-expression data. Further, we identify upregulation of a drug-detoxification pathway specifically in xenografts and cell lines of one of the subtypes. These models and data will help to better understand inter-patient heterogeneity in PDAC and identify novel drug targets and diagnostic markers.
Project description:To further development of our lncRNA and mRNA expression approach to pancreatic ductal adenocarcinoma(PDAC), we have employed lncRNA and mRNA microarray expression profiling as a discovery platform to identify lncRNA and mRNA expression in pancreatic ductal adenocarcinoma.Human pancreatic ductal adenocarcinoma tissues and normal pancreatic tissues from PDAC donors and other duodenum diseases donors.
Project description:Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers, but divergent outcomes are apparent between patients. To delineate the intertumor heterogeneity that contributes to this, we aimed to identify clinically distinct gene expression-based subgroups. From a cohort of 345 resected pancreatic cancer cases, 90 samples with confirmed diagnosis of PDAC and sufficient tumor content were available for gene expression analysis by RNA sequencing. Unsupervised classification was applied, and a classifier was constructed. Species-specific transcript analysis on matching patient-derived xenografts (PDX, N=14) allowed construction of tumor- and stroma-specific classifiers for use on PDX models and cell lines.
Project description:In this work, we reported a strategy to produce 3D in vitro microtissues of pancreatic ductal adenocarcinoma (PDAC) for studying the desmoplastic reaction activated by the stroma-cancer crosstalk. The purpose of this dataset was to examine the transcriptional expression changes of normal fibroblasts (NF), cancer-associated fibroblasts (CAF) and pancreatic adenocarcinoma cell line (PT45) in 3D versus 2D culture and in mono-culture versus co-culture. Illumina Human BeadChips were used to profile the transcriptome after 12 days of culture. We reported that human PDAC microtissues, obtained by co-culturing PT45 with NF or CAF within biodegradable microcarriers in spinner flask bioreactor, closely recapitulate key PDAC microenvironment characteristics.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor type with extremely high mortality (up to 92%) during 5 years after diagnosis. Here, cancer associated fibroblasts (CAF) from PDAC were compared to CAF from melanoma metastases (MELF) and to normal dermal fibroblasts (DF). The analysis was performed in three biological replicates for normal fibroblasts, eight biological replicates for PDAC CAF, and four biological replicates for melanoma CAF. Further technical replicates were used to improve data quality.
Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation. Pancreatic tissue from 4 groups of mice were used in this project: (1) the pancreas normal appearance of Pdx1-cre;KrasLSL-G12D;IKK2/beta mice, (2) the normal pancreas of Pdx1-cre;KrasLSL-G12D mice, (3) the pancreatic lesion of pancreatic intraepithelial neoplasia (PanIN) of Pdx1-cre;KrasLSL-G12D mice, and (4) the pancreatic lesion of PDAC of Pdx1-cre;KrasLSL-G12D mice. Each group included three mice. RNA samples from mouse pancreas were hybridized on GeneChip Mouse Gene 1.0 ST arrays (Affymetrix). Group (1) and group (2) were compared, and group (2), group (3) and group (4) were compared.
Project description:The ex vivo modelling of pancreatic ductal adenocarcinoma (PDAC) using patient-derived cells is a promising tool to predict treatment responses. Matrigel-based organoid and organotypic approaches are limited by their undefined molecular composition, hindering the recapitulation of the tumour’s characteristic desmoplasia, which is known to promote drug resistance. To overcome these limitations, we used self-assembling peptide amphiphiles (PAs) gelled in a minimal extracellular matrix to model the pancreatic tumour microenvironment and to establish 3D multicellular cultures of patient-derived PDAC cells, pancreatic stellate cells and macrophages. Matrisome analysis of 3D cultures demonstrated consistent ECM protein deposition, which was highly reminiscent of the corresponding primary PDAC tissues. The proteomic data obtained was also compared to the corresponding patient-derived xenografts (PDX) in nude mice and Matrigel-based cultures. Characterisation of the chemosensitivity of the cultures revealed realistic treatment responses by PDAC cells in PA hydrogels based on the responses of their corresponding PDX tumours. Histological, transcriptional and functional techniques confirmed these similarities, which were not observed in Matrigel-based cultures. These findings demonstrate the biomimetic nature of PA hydrogels, which enable cultured cells to recreate the PDAC matrisome ex vivo and to respond to chemotherapeutic agents in a predictive manner.