1162P - Transcriptomic analysis of gastroenteropancreatic neuroendocrine tumours with carcinoid syndrome

Background

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms arising from the diffuse endocrine system. Up to 30% of patients with advanced GEP-NETs develop carcinoid syndrome (CS), which negatively impacts quality of life and long-term survival. There is often a delay in the diagnosis of CS, and its management is challenging. A deeper understanding of the molecular landscape of GEP-NETs associated with CS could facilitate early diagnosis and potentially identify targetable molecules. In this context, we present a transcriptomic analysis of these tumours, including mRNAs related to the serotonin pathway and the tumor microenvironment, both relevant in the pathogenesis of the CS.

Methods

A total of 23 samples from advanced GEP-NET primaries and metastases (12 from patients with CS and 11 from patients without CS) underwent RNA extraction followed by gene expression analysis with Nanostring nCounter, including more than 1250 human mRNA. The identification of expressed genes was carried out using normalized data with the nSolver analysis software, allowing us to obtain hierarchical clustering of relevant pathways.

Results

There was statistically significant differences in the expression of genes involved in the regulation of the serotonin transporter and the cell cycle, between samples of GEP-NETs with and without CS. Subsequent analysis compared the expression profile of primary tumors and their metastases, revealing significant differences once again. Primary tumors were enriched in genes associated with tumor growth, angiogenesis, cell migration and tumor microenvironment.

Conclusions

The regulation of serotonin transport and the cell cycle may hold particular interest in patients with GEP-NETs and carcinoid syndrome. Genes involved in these processes could be investigated as potential diagnostic tools or therapeutic targets for this patient group. Furthermore, our findings suggest that there is molecular heterogeneity between primary tumours and their metastases in advanced GEP-NETs at a transcriptomic level, as has been described previously in other solid tumours.

Clinical trial identification

Editorial acknowledgement

Funding

GETNE (Spanish Society of Neuroendocrine and Endocrine Tumours).

Disclosure

All authors have declared no conflicts of interest.