Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer.

Autor:	Dansonka-Mieszkowska A; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Szafron LM; Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Moes-Sosnowska J; Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Kulinczak M; Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Balcerak A; Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Konopka B; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Kulesza M; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Budzilowska A; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Lukasik M; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Piekarska U; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Rzepecka IK; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Parada J; Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Zub R; Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Pienkowska-Grela B; Cytogenetics Laboratory, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Madry R; Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland., Siwicki JK; Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland., Kupryjanczyk J; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Apr 03; Vol. 9 (25), pp. 17735-17755. Date of Electronic Publication: 2018 Apr 03 (Print Publication: 2018).
DOI:	10.18632/oncotarget.24878
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.
Databáze:	MEDLINE
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