Apoptosome-dependent caspase activation proteins as prognostic markers in Stage II and III colorectal cancer
Apoptosome-dependent caspase activation proteins as prognostic markers in Stage II and III colorectal cancer
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DOI：
10.1038/bjc.2012.133
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发表时间：
2012-04-24
影响因子：
8.8
通讯作者：
Prehn, J. H. M.
中科院分区：
文献类型：
--
作者：
Hector, S.;Conlon, S.;Prehn, J. H. M.
背景：细胞凋亡的关键是细胞小体的形成和随后的半胱天冬酶的激活。该通路的缺陷在结直肠癌的发生和化疗耐药中具有重要作用;因此，肿瘤小体相关蛋白的表达可能与临床结果和对化疗的反应相关。在这里，我们进行了一个系统的免疫组化分析的关键蛋白参与的磷脂酶体依赖的半胱天冬酶激活（APAF 1、前半胱天冬酶9和3、SMAC和XIAP）在II期和III期结直肠癌患者队列中的作用，这些患者来自基于5-氟尿嘧啶的辅助化疗与仅术后观察的III期试验。生存分析表明，在本文研究的肿瘤小体相关蛋白中，胱天蛋白酶原3和APAF 1分别作为II期和III期结直肠癌的预测标志物具有潜在的临床实用性。有趣的是，我们确定APAF 1染色与更好的复发和接受chemotherapy.CONCLUSION的患者的总生存率相关：这些研究揭示的重要性的线粒体依赖的caspase激活途径，特别是前caspase 3和APAF 1蛋白，用于预测预后和治疗反应。英国癌症杂志（2012）106，1499-1505。doi：10.1038/bjc.2012.133 www.bjcancer.com在线发布2012年4月5日（C）2012英国癌症研究
BACKGROUND: Critical to successful execution of mitochondrial-mediated apoptosis is apoptosome formation and subsequent activation of caspases. Defects in this pathway have an important role in colorectal carcinogenesis and chemoresistance; therefore, the expression of apoptosome-associated proteins may be associated with clinical outcome and response to chemotherapy.METHODS: Here we performed a systematic analysis of the immunohistochemical expression of the key proteins involved in apoptosome-dependent caspase activation (APAF1, Pro-caspases 9 and 3, SMAC, and XIAP) in a cohort of Stage II and III colorectal cancer patients from a Phase III trial of adjuvant 5-fluorouracil-based chemotherapy vs postoperative observation alone.RESULTS: Survival analysis indicated that of the apoptosome-associated proteins examined here, Pro-caspase 3 and APAF1 have potential clinical utility as predictive markers in Stage II and III colorectal cancer, respectively. Interestingly, we identified APAF1 staining to be associated with better recurrence-free and overall survival in patients receiving chemotherapy.CONCLUSION: These studies reveal the importance of the apoptosome-dependent caspase activation pathway, specifically Pro-caspase 3 and APAF1 proteins, for predicting both prognosis and response to therapy. British Journal of Cancer (2012) 106, 1499-1505. doi:10.1038/bjc.2012.133 www.bjcancer.com Published online 5 April 2012 (C) 2012 Cancer Research UK