Z Gastroenterol 2019; 57(09): e258
DOI: 10.1055/s-0039-1695296
Leber und Galle
CCC und NET: Donnerstag, 03. Oktober 2019, 12:50 – 14:26, Studio Terrasse 2.1 A
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of gene expression changes associated with response to somatostatin analogues (SSAs) in gastrointestinal (GI) neuroendocrine tumors (NETs)

A Teufel
1   University of Heidelberg, Medical Faculty Mannheim, Department of Medicine II, Mannheim, Deutschland
,
K Evert
2   University of Regensburg, Institute of Pathologie, Regensburg, Deutschland
,
T Itzel
3   Universität Heidelberg, Medizinische Fakultät Mannheim, II. Medizinische Klinik, Mannheim, Deutschland
,
T Maass
4   Hepacult GmbH, Munich, Deutschland
,
C Koch
5   University of Frankfurt, Department of Medicine I, Frankfurt, Deutschland
,
M Vogelhuber
6   University of Regensburg, Department of Medicine III, Regensburg, Deutschland
,
N Schulte
1   University of Heidelberg, Medical Faculty Mannheim, Department of Medicine II, Mannheim, Deutschland
,
M Müller-Schilling
7   University of Regensburg, Department of Medicine I, Regensburg, Deutschland
,
T Gaiser
8   University of Heidelberg, Medical Faculty Mannheim, Department of Pathology, Mannheim, Deutschland
,
O Waidmann
5   University of Frankfurt, Department of Medicine I, Frankfurt, Deutschland
,
M Ebert
1   University of Heidelberg, Medical Faculty Mannheim, Department of Medicine II, Mannheim, Deutschland
,
M Evert
2   University of Regensburg, Institute of Pathologie, Regensburg, Deutschland
,
W Herr
6   University of Regensburg, Department of Medicine III, Regensburg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2019 (online)

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    Background:

    SSAs are commonly used to treat GI NETs as they have anti-secretory and antiproliferative effects. However, genetic markers predicting response to SSA are mostly lacking. We therefore performed a genome wide evaluation of gene expression changes associated with response to SSAs in GI NETs.

    Methods:

    RNA was extracted from FFPE conserved tumor tissue of 19 patients with NETs who previously received SSA treatment. Samples were hybridized against the human Clariom S Assays (Affymetrix). Data analysis was performed using the Bioconductor/R-package pd.clariom.s.human. Genes with at least 1,5-fold regulation and a p-value < 0,01 were considered significant. Pathway and functional analysis were performed using WebGestalt (2013 edition).

    Results:

    Comparing patients who had progression on SSA treatment versus long term stable patients, we identified 137 significantly regulated genes, including well established drivers of carcinogenesis in diverse cancers. Gene Ontology demonstrated an enrichment of “regulation of cell growth” (Observed vs. Expected ratio [O/E] R = 3.86; p = 0.0023; adjP = 0.0847). Further signaling pathway analysis demonstrated enrichment of Insulin signaling (O/E R = 7.88, p = 0.0067, adjP = 0.0189) and Jak-STAT (O/E ratio = 7.01; p = 0.0092, adjP = 0.0189) pathways. Finally, several disease associated signatures showed enrichment enriched, e.g. Immune System Diseases (O/E ratio = 4.26, p = 0.0006, adjP = 0.0248) or Pancreatic Diseases (O/E ratio = 9.86, p = 0.0008, adjP = 0.0248).

    Conclusion:

    Our explorative analysis of gene expression changes associated with response to SSAs in GI NETs identified promising molecular information to be further evaluated for predictive value in these tumors. An additional 14 patient samples are currently being investigated.


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