Aberrant expression of Wnt/β-catenin signaling pathway genes in aggressive malignant gastric gastrointestinal stromal tumors.
Aged
Aged, 80 and over
Cell Proliferation
DNA, Neoplasm
/ genetics
Female
Gastrointestinal Stromal Tumors
/ diagnosis
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Stomach Neoplasms
/ diagnosis
Wnt Proteins
/ biosynthesis
Wnt Signaling Pathway
beta Catenin
/ biosynthesis
FZD
Gene expression profiling
Malignant GIST
Wnt pathway
β-catenin
Journal
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
ISSN: 1532-2157
Titre abrégé: Eur J Surg Oncol
Pays: England
ID NLM: 8504356
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
20
01
2020
revised:
14
02
2020
accepted:
24
02
2020
pubmed:
10
3
2020
medline:
16
12
2020
entrez:
10
3
2020
Statut:
ppublish
Résumé
Recent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis. We investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands. GEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7. Wnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST.
Identifiants
pubmed: 32147424
pii: S0748-7983(20)30138-4
doi: 10.1016/j.ejso.2020.02.036
pii:
doi:
Substances chimiques
DNA, Neoplasm
0
Wnt Proteins
0
Wnt11 protein, human
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1080-1087Informations de copyright
Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no conflicts of interest.