Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients
Resumen: Introduction: There are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients.
Methods: KIT, PDGFRA, DOG1, IGF1R, MIR221 and MIR222 expression levels were determined by qRT-PCR. We also analyzed KIT and PDGFRA mutations, DOG1 expression, by immunohistochemistry, along with clinical and pathological data. Disease-free survival (DFS) and overall survival (OS) differences were calculated using Log-rank test.
Results: Hierarchical cluster analyses from gene expression data identified two groups: group I had KIT, DOG1 and PDGFRA overexpression and IGF1R underexpression and group II had overexpression of IGF1R and low expression of KIT, DOG1 and PDGFRA. Group II had a significant worse OS (p = 0.013) in all the series, and showed a tendency for worse OS (p = 0.11), when analyzed only the localized cases. MiRNA222 expression was significantly lower in a control subset of KIT-positive GIST (p < 0.001). OS was significantly worse in KNGL cases with higher expression of MIR221 (p = 0.028) or MIR222 (p = 0.014).
Conclusions: We identified two distinct KNGL subsets, with a different prognostic value. Increased levels of miRNA221/222, which are associated with worse OS, could explain the absence of KIT protein expression of most KNGL tumors.

Idioma: Inglés
DOI: 10.18632/oncotarget.24799
Año: 2018
Publicado en: Oncotarget 9, 25 (2018), 17576-17588
ISSN: 1949-2553

Factor impacto SCIMAGO: 1.575 - Oncology (Q1)

Tipo y forma: Article (Published version)
Área (Departamento): Area Anatom.Embriol.Humana (Dpto. Anatom.Histolog.Humanas)

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 Record created 2018-05-09, last modified 2019-11-26


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