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A single-cell transcriptomic comparison between small intestinal neuroendocrine tumors and their progenitor

Axling, F.; Barazeghi, E.; Hellman, P.; Norlen, O.; Backman, S.; Stalberg, P.

2025-02-15 cancer biology
10.1101/2025.02.10.637596 bioRxiv
Show abstract

Several studies have attempted to find the initiating drivers of small intestinal neuroendocrine tumors (SI-NET) development and the molecular mechanisms driving progression and metastatic spread. For gene expression studies using bulk microarrays and RNA sequencing, researchers commonly use normal intestinal mucosa as a control. The intestine is made up of several different cell types, and using bulk RNA-seq may generate findings that reflect factors other than the tumor transformation. This could potentially contribute to the lack of discoverable treatments and prevention strategies for SI-NETs. We performed scRNA-seq on tissue from two patients that had tumor resection surgery and separated the EC cells from the normal intestinal mucosa and used specific markers to compare them against SI-NET tumors cells. We pinpointed new genes associated with chr18 haploinsufficiency but also others with loss or gain of expression that have not previously been associated with SI-NETs, and which could be potential targets for further functional genomic studies.

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