Profiling of differentially expressed proteins in stage IV Colorectal cancers with good and poor outcomes
Profiling of differentially expressed proteins in stage IV Colorectal cancers with good and poor outcomes
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DOI：
10.1016/j.jprot.2011.12.002
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发表时间：
2012-06-06
影响因子：
3.3
通讯作者：
Lee, Cheolju
中科院分区：
文献类型：
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作者：
Kim, Hye-Jung;Kang, Un-Beom;Lee, Cheolju
筛查癌症复发高风险的患者将有助于获得更准确和个性化的治疗。在本研究中，我们尝试通过应用两种不同的定量蛋白质组学技术（差异凝胶电泳和可裂解同位素编码亲和标签方法）来鉴定与预后相关的蛋白质谱。从 IV 期结直肠癌 (CRC) 患者中获取 6 个肿瘤组织，其中 3 个在姑息手术和后续化疗后存活超过 5 年（良好预后组，GPG），另外 3 个在 25 个月内死亡（不良预后组，PPG）。从两次独立的定量分析中，我们鉴定了 175 个丰度比大于 2 倍的蛋白质。基因本体分析表明，PPG 中与细胞组装/组织和运动相关的蛋白质普遍增加。选择包括 Caveolin-1 在内的 22 种蛋白质通过蛋白质印迹和免疫组织化学进行验证性研究。使用曼-惠特尼检验分析每个单独蛋白质的蛋白质印迹数据，并通过逻辑回归分析生成多标记组。五种蛋白质，即脂肪酸结合蛋白 1、智力素 1、移行内质网 ATP 酶、转凝胶蛋白和原肌球蛋白 2，在两个预后组之间存在显着差异（置信度为 95%）。没有任何一种蛋白质能够完全区分这两个群体。然而，五种蛋白质的组合可以有效区分 PPG 和 GPG 患者 (AUC=1)。我们的研究表明，由蛋白质组特征组成的多标记物组可以提供准确的预测信息并可能有助于个性化治疗。本文是题为“蛋白质组学：临床联系”的特刊的一部分。 (C) 2011 Elsevier B.V. 保留所有权利。
Screening patients at high risk of recurrence of cancer would allow for more accurate and personalized treatment. In this study, we tried to identify the prognosis-related protein profile by applying two different quantitative proteomic techniques, difference in-gel electrophoresis and cleavable isotope-coded affinity tag method. Six tumor tissues were obtained from stage IV colorectal cancer (CRC) patients, of which three have survived more than five years (good prognostic group, GPG) and the other three died within 25 months (poor prognostic group, PPG) after palliative surgery and subsequent chemotherapy treatment. From the two independent quantitative analyses, we identified 175 proteins with abundance ratios greater than 2-fold. Gene ontology analysis revealed that proteins related to cellular assembly/organization and movement were generally increased in the PPG. Twenty-two proteins, including caveolin-1, were chosen for confirmatory studies by Western blot and immunohistochemistry. The Western blot data for each individual protein were analyzed with Mann-Whitney tests, and a multi-marker panel was generated by logistic regression analysis. Five proteins, fatty acid binding protein 1, intelectin 1, transitional endoplasmic reticulum ATPase, transgelin and tropomyosin 2, were significantly different between the two prognostic groups within 95% confidence. No single protein could completely distinguish the two groups from each other. However, a combination of the five proteins effectively distinguished PPG from GPG patients (AUC=1). Our study suggests a multi-marker panel composed of proteome signatures that provide accurate predictive information and potentially assist personalized therapy. This article is part of a Special Issue entitled: Proteomics: The clinical link. (C) 2011 Elsevier B.V. All rights reserved.