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. this dataset, describe the RNA sequencing data used in the multiomics study.
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.
Project description:RNA binding protein, Human Antigen R (HuR/ELAVL1), regulates mRNA stability of key species involved in pancreatic ductal adenocarcinoma (PDAC) cell survival under conditions of chemotherapeutic stress, hypoxia, low glucose environment. We used RNA immunoprecipitation-microarray or RNP-IP from cytoplasmic extracts of PDAC cell lines exposed to chemotherpaeutic stress (olaparib and gemcitabine) to evaluate whole transcriptome gene expression profile associated with HuR and find novel trargtes associated with DNA repair functions of HuR.
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:Expression profiling of 8 normal pancreatic and 14 PDAC tissues. Data was generated from Affymetrix arrays. Results provide a global profile of over 50,000 genes in normal and tumorous tissues, and comparison of the differentially expressed genes between the normal and tumor groups. Gene expression was profiled and compared between normal pancreatic and PDAC RNA samples globally, using Affymetrix GeneChip® Human Genome U133 Plus 2.0array.
Project description:RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) primary cultures from five different patient-derived xenograft models grown either in adherent conditions selecting for non-CSCs or in CSC-enriching anchorage-independent sphere conditions. A and B are two biological duplicates, from the same patient-derived xenograft model of PDAC.
Project description:A microarray was performed in order to screen the changes in gene expression following Lynx1 knockdown in 2 human PDAC cell lines Miapaca and BXPC3 and using two specific siRNA to Lynx1