Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Cell Mol Life Sci. 2012 Jan;69(2):325-33. doi: 10.1007/s00018-011-0752-0. Epub 2011 Jul 8.
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.
DNA 非整倍性已被确定为大多数上皮性恶性肿瘤的预后因素。我们旨在确定不同预后亚组子宫内膜癌中与倍性相关的蛋白表达。通过凝胶电泳比较正常子宫内膜 (n=5)、二倍体 (n=7) 和非整倍体 (n=7) 子宫内膜癌之间的蛋白表达模式，检测到 121 种与倍性相关的蛋白形式，42 种在正常子宫内膜和二倍体子宫内膜样癌之间差异表达，37 种在二倍体和非整倍体子宫内膜样癌之间差异表达，41 种在二倍体子宫内膜样癌和非整倍体子宫乳头状浆液癌之间差异表达。通过质谱鉴定蛋白质，并通过 Ingenuity Pathway Analysis 进行评估。通过液相色谱/质谱法确认靶标。质谱鉴定出 41 种不同的多肽，通路分析得出以波形蛋白和 NF-κB 为中心节点的高排名网络。这些结果确定了与倍性相关的蛋白表达差异，这些差异超过了组织病理学相关的表达差异，并强调了子宫内膜癌基因组稳定性中的特定蛋白网络。
