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Protein profiling of genomic instability in endometrial cancer
Authors:Gemoll Timo  Habermann Jens K  Lahmann Johanna  Szymczak Silke  Lundgren Caroline  Bündgen Nana K  Jungbluth Thomas  Nordström Britta  Becker Susanne  Lomnytska Marta I  Bruch Hans-Peter  Ziegler Andreas  Hellman Ulf  Auer Gert  Roblick Uwe J  Jörnvall Hans
Affiliation:Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Abstract:DNA aneuploidy has been identified as a prognostic factor in the majority of epithelial malignancies. We aimed at identifying ploidy-associated protein expression in endometrial cancer of different prognostic subgroups. Comparison of gel electrophoresis-based protein expression patterns between normal endometrium (n?=?5), diploid (n?=?7), and aneuploid (n?=?7) endometrial carcinoma detected 121 ploidy-associated protein forms, 42 differentially expressed between normal endometrium and diploid endometrioid carcinomas, 37 between diploid and aneuploid endometrioid carcinomas, and 41 between diploid endometrioid and aneuploid uterine papillary serous cancer. Proteins were identified by mass spectrometry and evaluated by Ingenuity Pathway Analysis. Targets were confirmed by liquid chromatography/mass spectrometry. Mass spectrometry identified 41 distinct polypeptides and pathway analysis resulted in high-ranked networks with vimentin and Nf-κB as central nodes. These results identify ploidy-associated protein expression differences that overrule histopathology-associated expression differences and emphasize particular protein networks in genomic stability of endometrial cancer.
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