Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer
| Autor: | Martyna Lukasik, Agnieszka Budzilowska, Jan Konrad Siwicki, Urszula Piekarska, Anna Balcerak, Iwona K. Rzepecka, Renata Zub, Bozena Konopka, Agnieszka Dansonka-Mieszkowska, Joanna Moes-Sosnowska, Lukasz Szafron, Joanna Parada, Barbara Pienkowska-Grela, Radoslaw Madry, Jolanta Kupryjanczyk, Mariusz Kulinczak, Magdalena Kulesza |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Single-nucleotide polymorphism chemotherapy polymorphism 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Gene knockdown Taxane business.industry EMSY Cytogenetics Single-strand conformation polymorphism medicine.disease Chemotherapy regimen 030104 developmental biology ovarian cancer Paclitaxel chemistry 030220 oncology & carcinogenesis gene expression Ovarian cancer business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Agnieszka Dansonka-Mieszkowska 1, * , Lukasz M. Szafron 2, * , Joanna Moes-Sosnowska 2 , Mariusz Kulinczak 2 , Anna Balcerak 3 , Bozena Konopka 1 , Magdalena Kulesza 1 , Agnieszka Budzilowska 1 , Martyna Lukasik 1 , Urszula Piekarska 1 , Iwona K. Rzepecka 1 , Joanna Parada 2 , Renata Zub 3 , Barbara Pienkowska-Grela 4 , Radoslaw Madry 5 , Jan K. Siwicki 2 and Jolanta Kupryjanczyk 1 1 Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland 2 Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland 3 Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland 4 Cytogenetics Laboratory, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland 5 Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland * These authors have contributed equally to this work Correspondence to: Agnieszka Dansonka-Mieszkowska, email: agnieszka.dansonka-mieszkowska@coi.pl Keywords: ovarian cancer; EMSY; polymorphism; gene expression; chemotherapy Received: March 31, 2017 Accepted: February 28, 2018 Published: April 03, 2018 ABSTRACT EMSY, a BRCA2–associated protein, is amplified and overexpressed in various sporadic cancers. This is the first study assessing the clinical impact of its expression and polymorphisms on ovarian cancer (OvCa) outcome in the context of the chemotherapy regimen used. In 134 frozen OvCa samples, we assessed EMSY mRNA expression with Reverse Transcription-quantitative PCR, and also investigated the EMSY gene sequence using SSCP and/or PCR-sequencing. Clinical relevance of changes in EMSY mRNA expression and DNA sequence was evaluated in two subgroups treated with either taxane/platinum (TP, n=102) or platinum/cyclophosphamide (PC, n=32). High EMSY expression negatively affected overall survival (OS), disease-free survival (DFS) and sensitivity to treatment (PS) in the TP-treated subgroup (p-values: 0.001, 0.002 and 0.010, respectively). Accordingly, our OvCa cell line studies showed that the EMSY gene knockdown sensitized A2780 and IGROV1 cells to paclitaxel. Interestingly, EMSY mRNA expression in surviving cells was similar as in the control cells. Additionally, we identified 24 sequence alterations in the EMSY gene, including the previously undescribed: c.720G>C, p.(Lys240Asn); c.1860G>A, p.(Lys620Lys); c.246-76A>G; c.421+68A>C. In the PC-treated subgroup, a heterozygous genotype comprising five SNPs (rs4300410, rs3814711, rs4245443, rs2508740, rs2513523) negatively correlated with OS (p-value=0.009). The same SNPs exhibited adverse borderline associations with PS in the TP-treated subgroup. This is the first study providing evidence that high EMSY mRNA expression is a negative prognostic and predictive factor in OvCa patients treated with TP, and that the clinical outcome may hinge on certain SNPs in the EMSY gene as well. |
| Databáze: | OpenAIRE |
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