Digital spatial profiling of pancreatic ductal adenocarcinoma, acinar ductal metaplasia and adjacent normal pancreas tissue

Pancreatic ductal adenocarcinoma (PDAC) is the most important histological subtype of pancreatic cancer, accounting for approximately 90% of all pancreatic cancers.Acinar to ductal metaplasia (ADM) is a recently recognized, yet less well-studied, precursor lesion of PDAC developed in the setting of chronic pancreatitis. Through digital spatial mRNA profiling, we compared ADM and adjacent PDAC tissues from patient samples to unveil the bridging genes, bridging signaling pathway and bridging molecular function during the malignant transformation of pancreatitis. Overall design: A total of 8 sets of PDAC tissue samples were obtained from 8 patients with a history of chronic pancreatitis who underwent surgical resection in McGill University Health Centre. In each case, formalin fixed paraffin embedded (FFPE) tissue blocks that contain normal acini, ADM tissue and PDAC on the same tissue section were selected. None of the patients with pancreatic cancer received any pre-operative treatments, including radiotherapy, chemotherapy, or biological treatments. All specimens were histopathologically diagnosed by two pathologists according to the WHO diagnostic criteria for PDAC. We selected several regions of interest (ROIs) from each PDAC sample, including normal, ADM and PDAC ROIs. NanoString Technologies' newly developed GeoMx digital spatial profiling (DSP) technology allows for morphology-driven, high-plex spatial analysis of FFPE samples. Using the GeoMx Cancer Transcriptome Atlas, a panel of RNA probes designed for comprehensive profiling of the tumor, tumor microenvironment, and tumor immune status with 1860 RNA targets, we directly analyzed the in situ RNA expression of a total of 48 ROIs from 8 PDAC samples.