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Title: Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients
Author: Moura, David S.
Ramos, Rafel
Fernandez-Serra, Antonio
Serrano Piñol, M. Teresa
Cruz, Julia
Alvarez-Alegret, Ramiro
Ortiz-Duran, Rosa
Vicioso, Luis
Gomez-Dorronsoro, Maria Luisa
García del Muro Solans, Xavier
Martinez-Trufero, Javier
Rubió Casadevall, Jordi
Sevilla, Isabel
Lainez, Nuria
Gutiérrez, Antonio
Serrano, César
Lopez-Alvarez, Maria
Hindi, Nadia
Taron, Miquel
López Guerrero, José Antonio
Martin-Broto, Javier
Keywords: RNA
Expressió gènica
Gene expression
Issue Date: 3-Apr-2018
Publisher: Impact Journals
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2018, vol. 9, num. 25, p. 17576-17588
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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