Investigating molecular mechanisms of canine Insulinoma progression using transcriptomic analysis

Pancreatic neuroendocrine tumours (PNETs) are the most common neuroendocrinetumours diagnosed in humans and dogs. Due to the highly heterogeneous nature ofthese tumours, definitive data are still lacking over the molecular mechanismsinvolved in their cancerous behaviour.This study focused on insulinoma (INS), as it is the most commonly diagnosedPNET in human and veterinary oncology. INS is an insulin-producing tumour thatcauses a hypoglycaemic syndrome related to the excessive insulin production. Inhumans, it is often a small benign neoplasm readily curable by surgical resectionwhereas, in dogs, INS is often malignant. Despite current treatment modalities,malignant canine and human INS have a poor prognosis as patients tend to developmetastases in liver and lymph nodes that do not respond to current therapies.To date, the mechanisms by which tumours spread and the clinical causes of chemoresistance remain only partially understood. From a comparative oncology perspective, the close resemblance of canine and human malignant INS makes canine INS an interesting study model for human INS.Here, RNA-sequencing analysis was performed over a small set of canine INS tumour samples in order to identify mechanisms involved in INS carcinogenesis through different stages of the disease. Data show that distinct gene profiles characterised early and late stage of canine INS. The combination of differential gene expression with pathway and network analyses represented a starting point into an in-depth understanding of this poorly studied cancer. These integrative computational approaches could be the key to future effective early cancer diagnosis and treatment planning in canine patients diagnosed with malignant INS.