Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients

Moura, D.S. ; Ramos, R. ; Fernandez-Serra, A. ; Serrano, T. ; Cruz, J. ; Alvarez-Alegret, R. (Universidad de Zaragoza) ; Ortiz-Duran, R. ; Vicioso, L. ; Gomez-Dorronsoro, M.L. ; del Muro, X.G. ; Martinez-Trufero, J. ; Rubio-Casadevall, J. ; Sevilla, I. ; Lainez, N. ; Gutierrez, A. ; Serrano, C. ; Lopez-Alvarez, M. ; Hindi, N. ; Taron, M. ; López-Guerrero, J.A. ; Martin-Broto, J.

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: Artículo (Versión definitiva)

Área (Departamento): Area Anatom.Embriol.Humana (Dpto. Anatom.Histolog.Humanas)