000070299 001__ 70299
000070299 005__ 20191126134634.0
000070299 0247_ $$2doi$$a10.18632/oncotarget.24799
000070299 0248_ $$2sideral$$a105775
000070299 037__ $$aART-2018-105775
000070299 041__ $$aeng
000070299 100__ $$aMoura, D.S.
000070299 245__ $$aGene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients
000070299 260__ $$c2018
000070299 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070299 5203_ $$aIntroduction: 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.
000070299 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000070299 592__ $$a1.575$$b2018
000070299 593__ $$aOncology$$c2018$$dQ1
000070299 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070299 700__ $$aRamos, R.
000070299 700__ $$aFernandez-Serra, A.
000070299 700__ $$aSerrano, T.
000070299 700__ $$aCruz, J.
000070299 700__ $$0(orcid)0000-0003-1038-8152$$aAlvarez-Alegret, R.$$uUniversidad de Zaragoza
000070299 700__ $$aOrtiz-Duran, R.
000070299 700__ $$aVicioso, L.
000070299 700__ $$aGomez-Dorronsoro, M.L.
000070299 700__ $$adel Muro, X.G.
000070299 700__ $$aMartinez-Trufero, J.
000070299 700__ $$aRubio-Casadevall, J.
000070299 700__ $$aSevilla, I.
000070299 700__ $$aLainez, N.
000070299 700__ $$aGutierrez, A.
000070299 700__ $$aSerrano, C.
000070299 700__ $$aLopez-Alvarez, M.
000070299 700__ $$aHindi, N.
000070299 700__ $$aTaron, M.
000070299 700__ $$aLópez-Guerrero, J.A.
000070299 700__ $$aMartin-Broto, J.
000070299 7102_ $$11003$$2027$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Anatom.Embriol.Humana
000070299 773__ $$g9, 25 (2018), 17576-17588$$pONCOTARGET$$tOncotarget$$x1949-2553
000070299 8564_ $$s499508$$uhttps://zaguan.unizar.es/record/70299/files/texto_completo.pdf$$yVersión publicada
000070299 8564_ $$s112977$$uhttps://zaguan.unizar.es/record/70299/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070299 909CO $$ooai:zaguan.unizar.es:70299$$particulos$$pdriver
000070299 951__ $$a2019-11-26-13:43:12
000070299 980__ $$aARTICLE