Spatial Transcriptomics of Perineural Invasion in Pancreatic Ductal Adenocarcinomas

Pancreatic Ductal Adenocarcinoma (PDAC) has a high incidence of perineural invasion (PNI), a pathological feature of cancer invasion of nerves. PNI is associated with poor prognosis, metastasis, local recurrence and cancer pain. It has been suggested that interactions between nerves and the tumour microenvironment (TME) play a role in the PDAC tumorigenesis, however our ability to study these interactions in patient samples has been technologically limited. Here we used Nanostring GeoMx Digital Spatial Profiler to analyze the whole transcriptome of the cancer and nerve compartments in PNI and non-PNI foci from 13 PDAC patients. We identified previously reported pathways involved in PNI, including Axonal Guidance , ROBO-SLIT Signaling supporting the study approach. Spatial transcriptomics highlighted the potential role of nerve and cancer cells in PNI foci in influencing the immune landscape of the TME and suggested similarities between PNI and nerve injury-response. This study revealed novel pathways, Endocannabinoid and Polyamine metabolism , which may contribute to PNI and cancer pain. These findings require additional in vitro and/or in vivo investigations to dissect the mechanism that Endocannabinoids and Polyamines may play in PNI and cancer growth. These pathways can be targeted providing a potential novel approach to treat PDAC.