A Quantitative Proteomic Approach of the Different Stages of Colorectal Cancer Establishes OLFM4 as a New Nonmetastatic Tumor Marker
A Quantitative Proteomic Approach of the Different Stages of Colorectal Cancer Establishes OLFM4 as a New Nonmetastatic Tumor Marker
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DOI：
10.1074/mcp.m111.009712-1
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发表时间：
2011-12-01
影响因子：
7
通讯作者：
Guette, Catherine
中科院分区：
文献类型：
--
作者：
Besson, Damien;Pavageau, Aude-Helene;Guette, Catherine
表达谱代表了新的分子工具，可用于表征肿瘤进展的连续步骤和预测复发或化疗反应。在这项研究中，我们使用定量蛋白质组学分析来比较不同阶段的结直肠癌。采用激光显微切割、OFFGEL分离、iTRAQ标记和MALDI-TOF/TOF MS技术对28例结直肠癌组织进行蛋白质组研究。两个软件包用于鉴定和定量差异表达的蛋白质：Protein Pilot和iQuantitator。基于类似于1，190，702 MS/MS谱，共鉴定了3138种蛋白质，这代表了迄今为止实现的最大的结直肠癌数据库，并证明了我们的定量蛋白质组学方法的价值。以这种方式，已经为每个患者和每个结肠直肠异型增生和癌症阶段（阶段I-IV）鉴定了个体蛋白质表达和变异。在不同的阶段中，总共有555种蛋白质呈现显著的倍数变化，并且这种差异表达与人类蛋白质图谱数据库中报道的免疫组织化学结果相关。为了确定结直肠癌早期阶段的候选生物标志物，我们将研究重点放在分泌蛋白上。通过这种方式，我们确定了嗅觉调节素-4，它在腺瘤和结直肠肿瘤的早期阶段过表达。在126例石蜡包埋组织中通过免疫组化证实了这种早期过度表达。我们的研究结果还表明OLFM 4受Ras-NF-κ B2途径的调节，Ras-NF-κ B2途径是结直肠肿瘤中失调的主要致癌途径之一。Molecular & Cellular Proteomics 10：10.1074/mcp. M111.009712，1-14，2011.
Expression profiles represent new molecular tools that are useful to characterize the successive steps of tumor progression and the prediction of recurrence or chemotherapy response. In this study, we have used quantitative proteomic analysis to compare different stages of colorectal cancer. A combination of laser microdissection, OFFGEL separation, iTRAQ labeling, and MALDI-TOF/TOF MS was used to explore the proteome of 28 colorectal cancer tissues. Two software packages were used for identification and quantification of differentially expressed proteins: Protein Pilot and iQuantitator. Based on similar to 1,190,702 MS/MS spectra, a total of 3138 proteins were identified, which represents the largest database of colorectal cancer realized to date and demonstrates the value of our quantitative proteomic approach. In this way, individual protein expression and variation have been identified for each patient and for each colorectal dysplasia and cancer stage (stages I-IV). A total of 555 proteins presenting a significant fold change were quantified in the different stages, and this differential expression correlated with immunohistochemistry results reported in the Human Protein Atlas database. To identify a candidate biomarker of the early stages of colorectal cancer, we focused our study on secreted proteins. In this way, we identified olfacto-medin-4, which was overexpressed in adenomas and in early stages of colorectal tumors. This early stage overexpression was confirmed by immunohistochemistry in 126 paraffin-embedded tissues. Our results also indicate that OLFM4 is regulated by the Ras-NF-kappa B2 pathway, one of the main oncogenic pathways deregulated in colorectal tumors. Molecular & Cellular Proteomics 10: 10.1074/mcp.M111.009712, 1-14, 2011.