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Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, Oncotarget, Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Biblos-e Archivo. Repositorio Institucional de la UAM, Digital.CSIC. Repositorio Institucional del CSIC
- Publication Year :
- 2018
- Publisher :
- Impact Journals, 2018.
-
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.<br />[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.<br />[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).<br />[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.<br />The project was funded by the Instituto de Salud Carlos III (ISCIII) - Fondo Europeo de Desarrollo Regional (FEDER), through a public competitive call (project reference PI15/01254; principal Investigator Javier Martín Broto), and the Spanish Group for Research on Sarcoma (GEIS).
- Subjects :
- 0301 basic medicine
Hematology department
medicine.medical_specialty
Patients
Group ii
Population
Protein expression
Valencian
03 medical and health sciences
0302 clinical medicine
IGF1R
Overall survival
Medicine
Pacients
education
education.field_of_study
GiST
business.industry
KNGL
miRNA221/222 cluster
KIT
Biología y Biomedicina / Biología
DOG1
Expressió gènica
language.human_language
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Family medicine
language
RNA
Catalan
Gene expression
business
Research Paper
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Dipòsit Digital de la UB, Universidad de Barcelona, Oncotarget, Zaguán. Repositorio Digital de la Universidad de Zaragoza, instname, Biblos-e Archivo. Repositorio Institucional de la UAM, Digital.CSIC. Repositorio Institucional del CSIC
- Accession number :
- edsair.doi.dedup.....eb28de91e70eca5046f358fd09338255