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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/178609
Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients
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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.
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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 GARCÍA, Antonio manuel, SERRANO, César, LOPEZ-ALVAREZ, Maria, HINDI, Nadia, TARON, Miquel, LÓPEZ GUERRERO, José antonio, MARTIN-BROTO, Javier. Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients. _Oncotarget_. 2018. Vol. 9, núm. 25, pàgs. 17576-17588. [consulta: 28 de gener de 2026]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/178609]