Molecular characterization of pancreatic neuroendocrine tumor tissue: characterization of altered pathways and potential non-invasive biomarkers

The study aimed to identify potential non-invasive biomarkers for pancreatic neuroendocrine tumours (PanNETs) through transcriptomic profiling of various tissue samples. The analysis encompassed samples from non-functional PanNETs (NF-PanNETs), insulinomas, and adjacent tumour tissues. In tumor vs. tumors adjacent pancreatic tissues differential expression analysis we identified 1210 differentially expressed genes (DEGs). Further pathway enrichment analysis revealed a multitude of overrepresented signaling pathways related to cell proliferation, survival and tumorigenesis. Notable findings were Beta-catenin independent and TCF dependent WNT signaling pathways, MAPK1/MAPK3 signaling and PIP3 activates AKT signaling. Amongst the list of DEGs we also identified 28 upregulated genes encoding for cell surface proteins and 24 upregulated genes encoding for cancer associated secretome proteins. Since the products of these genes are found in the bloodstream, there is a potential for further testing of these markers as biomarkers for liquid biopsy assay. Overall, the findings have underscored the promise of transcriptomic landscape analysis in identifying PanNET-specific non-invasive biomarkers and uncovering potential therapeutic targets. Overall design: To investigate changes in PanNET transcriptome compared to adjacent pancreatic tissues we performed whole transcriptome-based RNA-sequencing analysis for 30 tumor samples (17 grade I, 10 grade I, and three grade III tumors) and six tumor adjacent pancreatic tissue samples. The samples used were formalin-fixed paraffin-embedded tissue samples.