Survivin and XIAP expression in distinct tumor compartments of surgically resected gastric cancer: XIAP as a prognostic marker in diffuse and mixed type adenocarcinomas
Survivin and XIAP expression in distinct tumor compartments of surgically resected gastric cancer: XIAP as a prognostic marker in diffuse and mixed type adenocarcinomas
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DOI：
10.3892/ol.2017.6999
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Krieg, Andreas
中科院分区：
文献类型：
--
作者：
Dizdar, Levent;Tomczak, Monika;Krieg, Andreas
有相当多的证据表明，凋亡抑制蛋白（IAP）家族在肿瘤发生中发挥作用。研究最多的IAP家族成员，生存素和X连锁凋亡抑制剂（XIAP），已被证明是不同肿瘤实体的生物标志物。因此，本研究的目的是调查两种IAP在手术切除的胃癌（GC）标本的肿瘤中心，浸润前沿和淋巴结转移的表达水平。分析了含有来自201个原发性GC的样品的组织微阵列。采用免疫组化法检测IAP在不同肿瘤区室、正常黏膜和淋巴结转移灶中的表达。此外，研究了这些蛋白质的表达水平与临床病理学参数和总生存率之间的关系。高水平的生存素和XIAP在胃癌中是明显的，与正常粘膜相比，并与卵巢型和分化良好的胃癌，以及低国际抗癌联盟阶段。与相应的原发肿瘤相比，在淋巴结转移中检测到XIAP表达增加。XIAP过表达是弥漫型和混合型胃癌独立的阴性预后指标。这些结果表明，生存素和XIAP在胃癌发生的早期阶段的潜在作用。此外，淋巴结转移中增加的XIAP表达支持IAP在转移性肿瘤疾病中起重要作用的观察结果。由于XIAP的表达与弥漫型和混合型胃癌的生存率相关，因此XIAP可能成为这些类型胃癌的一个新的治疗靶点。
There is considerable evidence that the inhibitor of apoptosis protein (IAP) family serves a role in tumorigenesis. The most studied IAP family members, survivin and X-linked inhibitor of apoptosis (XIAP), have been demonstrated to serve as biomarkers in distinct tumor entities. Thus, the present study aimed to investigate the expression levels of both IAPs in the tumor center, invasion front and lymph node metastases of surgically resected gastric cancer (GC) specimens. Tissue microarrays containing samples from 201 primary GCs were analyzed. IAP expression was detected using immunohistochemistry in different tumor compartments, normal mucosa and lymph node metastases. In addition, the association between the expression levels of these proteins, and clinicopathological parameters and overall survival was investigated. High levels of survivin and XIAP were evident in GC, when compared with normal mucosa, and were correlated with intestinal-type and well-differentiated GC, as well as low International Union Against Cancer stages. Increased XIAP expression was detected in lymph node metastases as compared with corresponding primary tumors. XIAP overexpression was identified to be an independent negative prognostic marker in diffuse and mixed type GC. These results suggest a potential role of survivin and XIAP in the early phase of gastric carcinogenesis. In addition, increased XIAP expression in lymph node metastases supports the observation that IAPs serve an essential role in metastatic tumor disease. Since XIAP expression was identified to be associated with poor survival in diffuse and mixed type GC, XIAP may serve as a novel therapeutic target in these types of GC.