Functional transcriptomic annotation and protein–protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer

Autor: Alberto Ocaña, Eitan Amir, Atanasio Pandiella, Eva María Galán-Moya, Raquel Páez, Sandra Martinez-Canales, Balázs Győrffy, Miriam Nuncia-Cantarero, Miguel López de Rodas
Přispěvatelé: Instituto de Salud Carlos III, Diputación de Albacete, Fundación CRIS contra el Cáncer, Universidad de Castilla La Mancha, Acepain Albacete, European Commission
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
druggable proteins
Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Ovarian cancer
Clinical outcomes
Protein Interaction Mapping
Biomarkers
Tumor
Transcriptional regulation
medicine
Humans
Enhancer of Zeste Homolog 2 Protein
Gene Regulatory Networks
Radiology
Nuclear Medicine and imaging
Protein Interaction Maps
CHEK1
EZH2
Original Research
Cancer Biology
Neoplasm Staging
Ovarian Neoplasms
Cyclin-dependent kinase 1
Clinical outcome
Gene Expression Profiling
Druggable proteins
Gene Amplification
Molecular Sequence Annotation
Cell cycle
Prognosis
medicine.disease
Survival Analysis
Up-Regulation
Gene Expression Regulation
Neoplastic
Protein–protein interaction
protein–protein interaction
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Ubiquitin-Conjugating Enzymes
Cancer research
Female
Signal transduction
UBE2C
Zdroj: Digital.CSIC: Repositorio Institucional del CSIC
Consejo Superior de Investigaciones Científicas (CSIC)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Cancer Medicine
DOI: 10.13039/501100007480
Popis: © 2018 The Authors.
Although early stage ovarian cancer is in most cases a curable disease, some patients relapse even with appropriate adjuvant treatment. Therefore, the identification of patient and tumor characteristics to better stratify risk and guide rational drug development is desirable. Using transcriptomic functional annotation followed by protein–protein interacting (PPI) network analyses, we identified functions that were upregulated and associated with detrimental outcome in patients with early stage ovarian cancer. Some of the identified functions included cell cycle, cell division, signal transduction/protein modification, cellular response to extracellular stimuli or transcription regulation, among others. Genes within these functions included AURKA, AURKB, CDK1, BIRC5, or CHEK1 among others. Of note, the histone-lysine N-methyltransferase (EZH2) and the ubiquitin-conjugating enzyme E2C (UBE2C) genes were found to be upregulated and amplified in 10% and 6% of tumors, respectively. Of note, EZH2 and UBE2C were identified as principal interacting proteins of druggable networks. In conclusion, we describe a set of genes overexpressed in ovarian cancer with potential for therapeutic intervention including EZH2 and UBE2C.
This work has been funded by Instituto de Salud Carlos III (PI16/01121), Diputación de Albacete and CRIS Cancer Foundation (to AO) and the framework agreement between University of Castilla-La Mancha and Albacete Provincial Council (UCLM-Excma. Diputación de Albacete) in support to research activity (to EMGM). We would like to also thanks to the cancer associations AMUMA and ACEPAIN for supporting part of this work. EMGM is funded by the implementation research program of the UCLM (UCLM resolution date: 31/07/2014), with a contract for accessing the Spanish System of Science, Technology and Innovation-Secti (cofunded by the European Commission/FSE funds).
Databáze: OpenAIRE
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