Research for signal transduction factors in carcinogenesis by differential proteomics analysis

在这项研究中，低分子量蛋白质组，肽穹窿，是该疾病潜在生物标志物的来源。然而，在以往的报道中，几乎所有检测到的多肽都是来源于大量血浆蛋白的片段，可能是通过采集血液中疾病相关蛋白酶的活性以及体外凝血和补体降解途径产生的。此外，血液中丰富的主要血浆蛋白掩盖了指示疾病状态的循环肽生物标志物的存在，这使得发现此类生物标志物具有挑战性。在目前的研究中，我们建立了鉴别和定量血清肽分析的方法，这是有效的发现这些肽。采用二维LC-MALDI-TOF质谱进行综合分离、非标记定量和多样品比较数据分析。许多报告声称使用表面增强激光解吸/电离(SELDI)-TOF质谱或MALD…更多的I-TOF质谱已经确定了质量峰或质量峰组合，能够以高灵敏度和特异性诊断疾病。然而，这些研究大多是基于模式的，没有识别每一个这样的质量峰，因此，目前的分析平台必须是差异蛋白质组学的有力工具，以揭示致癌和癌症进展中的信号通路。我们还分析了肾透明细胞癌中涉及肿瘤进展和耐药的信号通路。目的：鉴定透明细胞肾细胞癌（CRCC）进展过程中的基因组改变，了解肾细胞的致癌途径。收集23例肿瘤及其相应的正常组织，分离基因组DNA和RNA。使用50 K SNP图谱阵列U133 Plus 2.0。分析了染色体上的个体拷贝数和相应位点上的基因表达模式。我们利用SNP阵列在肾细胞癌中发现了包括CXXC4在内的4q24的新型纯合缺失。CXXC4基因编码Idax蛋白，其功能是通过结合Dvl的PDZ结构域作为Wnt信号的负调节因子。在这里，我们报道了CXXC4在RCC发生和进展中的可能作用。目前的数据表明，CXXC4的减少可能在RCC的肿瘤进展中起重要作用。它在RCC中的缺失可能导致组成性激活Writ信号，并诱导β -连环蛋白下游功能基因的表达。少

In this study, the low-molecular-weight proteome, peptidome, is a source of potential biomarkers for the disease. However, almost all detected peptides in previous reports are fragments originating from highly abundant plasma proteins, probably through the activities of disease-associated proteases and the ex vivo coagulation and complement degradation pathways in the collected blood. In addition, the major plasma proteins abundant in blood mask the presence of circulating peptide biomarkers indicative of the disease state, making the discovery of such biomarkers challenging. In present study, we established the methodology for differential and quantitative serum peptidome profiling that is efficient in the discovery of these peptides. Comprehensive fractionation by 2 dimensional LC-MALDI-TOF MS, non-labeling quantification and multi-sample comparison data analysis were performed. Numerous reports claim that the use of surface-enhanced laser desorption/ionization (SELDI)-TOF MS or MALD … More I-TOF MS has identified mass peaks or combinations of mass peaks that are capable of diagnosing disease with high sensitivity and specificity. However, most of these studies are pattern-based without identification of each of such mass peaks and, therefore, present analytical platform must be powerful tool for differential proteomics to reveal signaling pathways in carcinogenesis and cancer progression. We also analyzed signaling pathways involved in cancer progression and drug-resistance in clear cell carcinoma of kidney. To identify genomic alterations involved in progression of clear cell renal cell carcinoma (CRCC) and figure out the oncogenic pathways of renal cell. Twenty-three tumors and their corresponding normal tissues were collected and genomic DNA and RNA were isolated. The 50 K SNP mapping array U133 Plus 2.0 array was used. Individual copy numbers on chromosome and gene expression patterns at corresponding loci were analyzed. We have identified novel homozygous deletion at 4q24 including CXXC4 by using SNP array in renal cell carcinoma. The CXXC4 gene encodes the Idax protein that whose functions as is a negative regulator of the Wnt signaling by binding to the PDZ domain of Dvl Here we report a possible role of CXXC4 in development and progression of RCC. Present data suggest that the decrease of CXXC4 might play an important role for tumor progression in RCC. Its loss in RCC may result in constitutively activate Writ signaling, and induce the expression of genes that function downstream of beta-catenin. Less