Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers

BMC Cancer

Research Article

Heidi Fiegl¹  Daniel Reimer¹  Gabriel Schmid¹  Annamarie Wiedemair¹  Julia Rössler¹  Christian Marth¹  Alain Gustave Zeimet¹  Sara Notaro² 

[1] Department of Obstetrics and Gynecology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria;Department of Obstetrics and Gynecology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria;Department of Gynecology and Obstetrics, University of Brescia, P.zza Spedali Civili 1, 25123, Brescia, Italy;

关键词: Ovarian cancer;    Folate receptor 1;    FOLR1;    FOLR1 promoter methylation;    Global DNA hypomethylation;    Type I;    Type II;    Platinum sensitivity;   

DOI  :  10.1186/s12885-016-2637-y

 received in 2015-08-14, accepted in 2016-07-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIn this retrospective study we evaluated the respective correlations and clinical relevance of FOLR1 mRNA expression, FOLR1 promoter specific methylation and global DNA hypomethylation in type I and type II ovarian cancer.MethodsTwo hundred fifty four ovarian cancers, 13 borderline tumours and 60 samples of healthy fallopian epithelium and normal ovarian epithelium were retrospectively analysed for FOLR1 expression with RT-PCR. FOLR1 DNA promoter methylation and global DNA hypomethylation (measured by means of LINE1 DNA hypomethylation) were evaluated with MethyLight technique.ResultsNo correlation between FOLR1 mRNA expression and its specific promoter DNA methylation was found neither in type I nor in type II cancers, however, high FOLR1 mRNA expression was found to be correlated with global DNA hypomethylation in type II cancers (p = 0.033). Strong FOLR1 mRNA expression was revealed for Grades 2-3, FIGO stages III-IV, residual disease > 0, and serous histotype. High FOLR1 expression was found to predict increased platinum sensitivity in type I cancers (odds ratio = 3.288; 1.256-10.75; p = 0.020). One-year survival analysis showed in type I cancers an independent better outcome for strong expression of FOLR1 in FIGO stage III and IV. For the entire follow up period no significant independent outcome for FOLR1 expression was revealed. In type I cancers LINE 1 DNA hypomethylation was found to exhibit a worse PFS and OS which were confirmed to be independent in multivariate COX regression model for both PFS (p = 0.026) and OS (p = 0.012).ConclusionNo correlations were found between FOLR1 expression and its specific promoter methylation, however, high FOLR1 mRNA expression was associated with DNA hypomethylation in type II cancers. FOLR1 mRNA expression did not prove to predict clinical outcome in type II cancers, although strong FOLR1 expression generally denotes ovarian cancers with highly aggressive phenotype. In type I cancers, however, strong FOLR1 expression has been found to be a reliable indicator of improved platinum responsiveness reflecting a transient better one-year follow up outcome in highly FOLR1 expressing type I cancers. An independent prognostic role of global DNA hypomethylation was demonstrated in type I tumours.

【 授权许可】

CC BY   
© The Author(s). 2016