Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer
PBN-AR
Instytucja
Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Oncotarget (40pkt w roku publikacji)
ISSN
1949-2553
EISSN
Wydawca
DOI
URL
Rok publikacji
2018
Numer zeszytu
25
Strony od-do
17735-17755
Numer tomu
9
Identyfikator DOI
Liczba arkuszy
21
Słowa kluczowe
en
ovarian cancer
EMSY
polymorphism
gene expression
chemotherapy
Streszczenia
Język
en
Treść
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.
Inne
System-identifier
COI55b8956e7cb543fcbafa4c4b7688e803
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