Fig. 3 | Scientific Reports

Fig. 3

From: Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression

Fig. 3

siNET gene expression resembles enteroendocrine cells. For deconvolution of tumor and non-tumor gene expression signatures independent component analysis was performed. (a) Independent component 3 of siNET expression anti-correlates with tumor cell content and (b) is depleted in REST target genes (GO-BP gene ontology biological process, TF transcription factor, p-values are adjusted using the Benjamini–Hochberg procedure). The top enriched gene set are shown (Supplementary Table 5). (c) REST gene expression negatively correlates with tumor cell content and is therefore downregulated in siNETs. (d) Western Blot analysis of REST in normal tissue (tonsil and healthy small intestine) and siNET tissue of 3 samples from our cohort and 6 independent samples (P primary tumor, MH hepatic metastasis). (e) Marker genes that define EEC cell-type signature. (f, g) siNET gene expression was deconvoluted using NMF. (f) NMF factor 4 correlated with siNET marker genes, (g) resembles the EEC cell-type signature and (h) is associated with tumor cell content. (i) Expression of REST and Synaptophysin (SYP) in intestinal epithelial cells (j) Gene expression of EEC subtype markers in siNETs implicates enterochromaffin cells as potential cell-of-origin.

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