Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Cell Mol Life Sci. 2011 Oct;68(19):3261-74. doi: 10.1007/s00018-011-0628-3. Epub 2011 Feb 3.
DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n=19), diploid (n=31), and aneuploid (n=47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.
DNA 非整倍性已被确定为上皮性恶性肿瘤的预后因素。进一步了解 DNA 非整倍性转化为蛋白质表达，将有助于确定新的生物标志物，以改善治疗效果和预后。采用图像细胞仪评估 DNA 倍性。通过凝胶电泳比较三种二倍体和四种非整倍体结直肠癌细胞系的蛋白质表达模式，检测到 64 个与倍性相关的蛋白质。通过质谱鉴定蛋白质，并进行 Ingenuity Pathway Analysis，得到两个重叠的高排名网络，维持细胞组装和组织、细胞周期以及细胞生长和增殖。在细胞系中通过 Western blot 对 CAPZA1、TXNL1 和 HDAC2 进行了显著验证，后两者在使用正常黏膜(n=19)、二倍体(n=31)和非整倍体(n=47)癌的组织微阵列的临床样本中也显示出表达差异。结果表明，影响 TXNL1 和 HDAC2 的不同蛋白质表达模式将预后不良的非整倍体与二倍体结直肠癌区分开来。
