The Clinical Effect of the Inhibitor of Apopotosis Protein Livin in Melanoma
The Clinical Effect of the Inhibitor of Apopotosis Protein Livin in Melanoma
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DOI：
10.1159/000334234
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发表时间：
2012-01-01
期刊：
影响因子：
3.5
通讯作者：
Kadouri, Luna
中科院分区：
文献类型：
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作者：
Lazar, Itay;Perlman, Riki;Kadouri, Luna
目的：凋亡抑制蛋白(IAP)Livin在黑色素瘤中经常过表达。Livin结合半胱氨酸天冬氨酸酶从而抑制细胞凋亡。我们发现，caspase裂解Livin产生一种截断形式，具有矛盾的促凋亡活性。方法：我们评估了114名接受自体黑色素瘤疫苗治疗的黑色素瘤患者的Livin表达与生存的相关性。在52例患者中，切除后无疾病证据(NED)，62例仍有活动期疾病(WAD)。用蛋白质印迹法检测蛋白质水平。结果：114例乳腺癌组织中有44例(38.4%)有Livin蛋白表达。在高Livin蛋白水平的NED患者中，中位总生存期为1.4年，在那些低-中等水平且不表达Livin的患者中，中位生存期为8.4年(p=0.025)。在高水平Livin蛋白表达的WAD患者中，相应的总生存期为2.3年，在中低水平患者中为11.3年，而在不表达Livin蛋白的患者中，矛盾的是，仅为4.0年(p=0.012)。结论：Livin蛋白的表达可能在黑色素瘤的发生发展中起一定作用，并与患者的生存密切相关。高水平的蛋白质与预后不良有关。然而，在WAD患者中，低到中等水平的Livin，而不是缺乏该蛋白，与良好的预后相关。这可能是由于这种重要的细胞凋亡调节因子具有矛盾的促凋亡活性。版权所有(C)2012 S.Karger AG，巴塞尔
Objective: The inhibitor of apoptosis protein (IAP) livin is frequently overexpressed in melanoma. Livin binds caspases and thereby inhibits apoptosis. We found that caspases cleave livin to produce a truncated form with a paradoxical proapoptotic activity. Methods: We assessed the correlation of livin expression with survival among 114 melanoma patients treated with an autologous melanoma vaccine. In 52 patients, resection resulted in no evidence of disease (NED) and 62 remained with active disease (WAD). Protein levels were assessed using Western blot. Results: We found livin protein expression in 44/114 samples (38.4%). Median overall survival was 1.4 years in NED patients with high levels of livin protein, 8.4 years in those with low-intermediate levels and not reached in patients who did not express livin (p = 0.025). The corresponding overall survival was 2.3 years among WAD patients with high levels of livin protein, 11.3 years in those with low-intermediate levels and, paradoxically, only 4.0 years in patients who did not express livin (p = 0.012). Conclusion: Livin protein expression may play a role in the progression of melanoma and correlates with survival. A high level of the protein is associated with a poor prognosis. However, in WAD patients low to intermediate level of livin, rather than absence of the protein, is associated with a favorable prognosis. This is probably due to the paradoxical proapoptotic activity of this important regulator of apoptosis. Copyright (C) 2012 S. Karger AG, Basel