Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location, and poor prognosis.
Artikel i vetenskaplig tidskrift, 2011

In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on 9 tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, PDGFRA, or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, P=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, NIH risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.

CD133 (prominin-1)

biomarker

GIST

expression profiling

KIT

Författare

Gabriella Arne

Göteborgs universitet

Erik Kristiansson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Olle Nerman

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Lars-Gunnar Kindblom

Royal Orthopaedic Hospital, NHS Foundation Trust

Håkan Ahlman

Göteborgs universitet

Bengt E Nilsson

Göteborgs universitet

Ola Nilsson

Göteborgs universitet

International Journal of Cancer

0020-7136 (ISSN) 1097-0215 (eISSN)

Vol. 129 5 1149-1161

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1002/ijc.25755

PubMed

21064103

Mer information

Skapat

2017-10-06