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Göteborgs universitets publikationer

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets.

Författare och institution:
Ellinor Andersson (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Yvonne Arvidsson (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Christina Swärd (Institutionen för kliniska vetenskaper, sektionen för kirurgi och kirurgisk gastroforskning, Avdelningen för kirurgi); Tobias Hofving (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center); Bo Wängberg (Institutionen för kliniska vetenskaper, sektionen för kirurgi och kirurgisk gastroforskning, Avdelningen för kirurgi); Erik Kristiansson (Institutionen för matematiska vetenskaper, Chalmers/GU); Ola Nilsson (Institutionen för biomedicin, avdelningen för patologi & Sahlgrenska Cancer Center)
Publicerad i:
Modern Pathology, 29 ( 6 ) s. 616-629
ISSN:
0893-3952
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
We wanted to define the transcriptome of small intestinal neuroendocrine tumors in order to identify clinically relevant subgroups of tumors, prognostic markers and novel targets for treatment. Genome-wide expression profiling was conducted on tumor biopsies from 33 patients with well-differentiated neuroendocrine tumors of the distal ileum and metastatic disease at the time of diagnosis. Unsupervised hierarchical clustering analysis identified three groups of tumors. The largest group, comprising half of the tumors, was characterized by longer patient survival and higher expression of neuroendocrine markers, including SSTR2. Tumors with higher grade (G2/3) or gain of chromosome 14 were associated with shorter patient survival and increased expression of cell cycle-promoting genes. Pathway analysis predicted the prostaglandin E receptor 2 (PTGER2) as the most significantly activated regulator in tumors of higher grade, whereas Forkhead box M1 (FOXM1) was the most significantly activated regulator in tumors with gain of chromosome 14. Druggable genes identified from expression profiles included clinically proven SSTR2 and also novel targets, for example, receptor tyrosine kinases (RET, FGFR1/3, PDGFRB and FLT1), epigenetic regulators, molecular chaperones and signal transduction molecules. Evaluation of candidate drug targets on neuroendocrine tumors cells (GOT1) showed significant inhibition of tumor cell growth after treatment with tyrosine kinase inhibitors or inhibitors of HDAC, HSP90 and AKT. In conclusion, we have defined the transcriptome of small intestinal neuroendocrine tumors and identified novel subgroups with clinical relevance. We found specific gene expression patterns associated with tumor grade and chromosomal alterations. Our data also suggest novel prognostic biomarkers and therapies for these patients.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Kirurgi
Postens nummer:
233347
Posten skapad:
2016-03-17 10:23
Posten ändrad:
2016-07-06 13:40

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