Transcriptomic analysis of patient-derived ex vivo models of pancreatic cancer

The aim of this study is to compare the transcriptomic profiles of various ex vivo models of pancreatic cancer. First, primary tumours and their corresponding xenografts in nude mice were analysed by RNA-seq. Monocultures of pancreatic cancer cells derived from the xenografts were then prepared as 2D monolayers, Matrigel-embedded organoids, spheres in suspension and 3D cultures in self-assembling peptide amphiphile (PA) hydrogels. Seven-day cultures were then analysed by RNA-seq. The results suggest that all ex vivo monocultures retain patient-specific transcriptional profiles, especially cancer stem cell signatures, while being deficient in the expression of stromal components such as the core matrisome. Correlations with the primary tumours were generally higher in PA hydrogels than organoids. Biased gene expression signatures were identified in certain models. This is the first study to explore the transcriptomic signatures of four different ex vivo models matched to their primary tumours of origin. 29 patient-matched pancreatic adenocarcinoma (PDAC) samples were analysed: three primary PDAC tumour samples, six PDAC monocultures in PA (3 patients, duplicates), six PDAC organoid monocultures in Matrigel (3 patients, duplicates), six PDAC monocultures in 2D (3 patients, duplicates), six PDAC monocultures in suspension (3 patients, duplicates), and two primary patient-derived xenografts in grown in nude mice.