Zhu Yi, Wu Rong, Sangha Navneet, Yoo Chul, Cho Kathleen R, Shedden Kerby A, Katabuchi Hidetaka, Lubman David M
Department of Chemistry, The University of Michigan, Ann Arbor, MI, USA.
Proteomics. 2006 Nov;6(21):5846-56. doi: 10.1002/pmic.200600165.
Ovarian cancer is a morphologically and biologically heterogeneous disease. The identification of type-specific protein markers for ovarian cancer would provide the basis for more tailored treatments, as well as clues for understanding the molecular mechanisms governing cancer progression. In the present study, we used a novel approach to classify 24 ovarian cancer tissue samples based on the proteomic pattern of each sample. The method involved fractionation according to pI using chromatofocusing with analytical columns in the first dimension followed by separation of the proteins in each pI fraction using nonporous RP HPLC, which was coupled to an ESI-TOF mass analyzer for molecular weight (MW) analysis. A 2-D mass map of the protein content of each type of ovarian cancer tissue samples based upon pI versus intact protein MW was generated. Using this method, the clear cell and serous ovarian carcinoma samples were histologically distinguished by principal component analysis and clustering analysis based on their protein expression profiles and subtype-specific biomarker candidates of ovarian cancers were identified, which could be further investigated for future clinical study.
卵巢癌是一种在形态学和生物学上具有异质性的疾病。鉴定卵巢癌类型特异性蛋白质标志物将为更具针对性的治疗提供基础,同时也为理解控制癌症进展的分子机制提供线索。在本研究中,我们采用了一种新方法,根据每个样本的蛋白质组模式对24个卵巢癌组织样本进行分类。该方法包括在第一维使用分析柱通过聚焦层析按等电点进行分级分离,随后使用无孔反相高效液相色谱对每个等电点级分中的蛋白质进行分离,该色谱与电喷雾离子化飞行时间质谱仪联用进行分子量(MW)分析。生成了基于等电点与完整蛋白质分子量的每种类型卵巢癌组织样本蛋白质含量的二维质谱图。使用该方法,通过主成分分析和聚类分析,根据其蛋白质表达谱在组织学上区分了透明细胞和浆液性卵巢癌样本,并鉴定了卵巢癌亚型特异性生物标志物候选物,可在未来的临床研究中进一步研究。