Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes

Abstract

BackgroundIn addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups.MethodsDNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16) or aneuploid (n = 9), and all uterine papillary serous cancers (UPSC) to be aneuploid (n = 8). All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA) and were correlated to protein expression changes.ResultsComparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization.ConclusionsWe conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.

Annexin‐A2 as predictor biomarker of recurrent disease in endometrial cancer

“…The increased expression of ANXA2 in NEEC in comparison with EEC raised the possibility that the elevated expression of ANXA2 in recurrent tumors could be due to the more frequent presence of NEEC among recurrent tumors, since NEEC is associated with aneuploidy and increase of recurrence. To rule out this possibility, we decided to evaluate the association of ANXA2 immunoexpression with the risk of recurrences, exclusively in EEC samples.…”

Endometrial receptivity array: Clinical application

“…The human endometrial transcriptome has been studied in women with a gynecological disease such as endometriosis and cancer. [ 18 19 ] Studies on the transcriptomics of human ER also gained impetus and ER transcriptome was studied in the natural cycle[ 20 ] and recurrent implantation failure (RIF). [ 21 22 ] Gene expression patterns have also been defined during controlled ovarian stimulation (COS) and hormonal replacement therapy (HRT) cycles.…”

Human Endometrial Transcriptomics: Implications for Embryonic Implantation

“…Endometrial transcriptomic profiles have also been investigated under different controlled ovarian stimulation protocols (Simon et al 2005;Horcajadas et al 2008), or in the context of unexplained pathologies such as recurrent implantation failure (Tapia et al 2008;Koler et al 2009;Altmäe et al 2010), or other endometrial conditions (Table 1) (Habermann et al 2011;Matsuzaki 2011). Most of these studies investigate the transcriptomic signature in the whole endometrial tissue without separating the different compartments.…”