Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma
Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma
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DOI：
10.1016/j.jprot.2011.11.030
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发表时间：
2012-02-16
影响因子：
3.3
通讯作者：
Kondo, Tadashi
中科院分区：
文献类型：
--
作者：
Morofuji, Noriaki;Ojima, Hidenori;Kondo, Tadashi
胆管癌是全球最致命的恶性肿瘤之一。近期研究报道，吉西他滨治疗在延长生存期方面有效。然而，由于该治疗仅使一部分患者受益，因此在治疗前需要对患者进行筛选。为了发现可预测胆管癌对吉西他滨治疗反应的生物标志物，我们检测了三种材料来源的蛋白质组：10个细胞系、9个异种移植物以及9个手术切除的原发性肿瘤，这些肿瘤来自对吉西他滨治疗反应不同的患者。双向差异凝胶电泳生成了包括3571个蛋白质斑点的定量蛋白质表达谱。我们检测到172个蛋白质斑点与对吉西他滨治疗的反应显著相关。通过质谱法鉴定了与这172个蛋白质斑点相对应的所有蛋白质。我们发现巨噬细胞加帽蛋白（CapG）在所有三种材料来源中都与对吉西他滨治疗的反应相关。在另外196例胆管癌病例中进行的免疫组织化学验证显示，CapG表达与淋巴管浸润状态和总生存期相关。多变量分析表明，CapG蛋白表达是总生存期的一个独立预后因素。总之，CapG被确定为一种新的候选生物标志物，可用于预测胆管癌对吉西他滨治疗的反应和生存期。（C）2011爱思唯尔有限公司。保留所有权利。
Cholangiocarcinoma is one of the deadliest malignancies worldwide. Recent studies reported that treatment with gemcitabine was effective in prolonging survival. However, as the treatment only benefited a limited subset of patients, selection of patients before treatment is required. To discover biomarkers predictive of the response to gemcitabine treatment in cholangiocarcinoma, we examined the proteome of three types of material resource; ten cell lines, nine xenografts and nine surgically resected primary tumors from patients who exhibited different response to gemcitabine treatment. Two-dimensional difference gel electrophoresis generated quantitative protein expression profiles including 3571 protein spots. We detected 172 protein spots with significant correlation with response to gemcitabine treatment. All proteins corresponding to these 172 protein spots were identified by mass spectrometry. We found that the macrophage-capping protein (CapG) was associated with response to gemcitabine treatment in all three types of material source. Immunohistochemical validation in an additional set of 196 cholangiocarcinoma cases revealed that CapG expression was associated with lymphatic invasion status and overall survival. Multivariate analysis showed that CapG protein expression was an independent prognostic factor for overall survival. In conclusion, CapG was identified as a novel candidate biomarker to predict response to gemcitabine treatment and survival in cholangiocarcinoma. (C) 2011 Elsevier B.V. All rights reserved.