Loss of ARID1A Expression is Related to Gastric Cancer Progression, Epstein-Barr Virus Infection, and Mismatch Repair Deficiency
Loss of ARID1A Expression is Related to Gastric Cancer Progression, Epstein-Barr Virus Infection, and Mismatch Repair Deficiency
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DOI：
10.1097/pai.0000000000000199
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发表时间：
2016-05-01
影响因子：
1.6
通讯作者：
Kim, Woo Ho
中科院分区：
文献类型：
--
作者：
Han, Nayoung;Kim, Min A.;Kim, Woo Ho
富含AT的相互作用结构域1A（ARID 1A）基因编码开关/蔗糖不可发酵（SWI-SNF）染色质重塑复合物的成员，并且被认为与p53协同作用作为肿瘤抑制因子。我们研究了胃癌（GC）中ARID 1A蛋白表达的临床意义，并研究了其与EB病毒相关（EBV）GC、错配修复（MMR）缺陷和p53改变的关系。我们使用组织芯片对417例胃癌标本进行了ARID 1A免疫组化。用EBV编码的小RNA原位杂交检测EBV感染。采用免疫组织化学方法对MMR蛋白缺陷和p53改变进行评估，并对微卫星不稳定状态进行评估。ARID 1A在胃癌组织中的表达缺失率为21.1%（88/417），而在胃腺瘤组织和非肿瘤性胃粘膜组织中均未观察到ARID 1A的表达缺失。ARID 1A基因缺失与pTNM分期、肿瘤浸润深度呈正相关（P分别为0.029和0.001）。在野生型p53组中，ARID 1A表达的丧失显著影响总生存率（P=0.016，对数秩检验）。此外，ARID 1A缺失与EBV阳性、MMR蛋白表达缺失和微卫星不稳定性高状态显著相关（P=0.028，
The AT-rich interactive domain 1A (ARID1A) gene encodes a member of the switch/sucrose nonfermentable (SWI-SNF) chromatin remodeling complex, and is considered to work as a tumor suppressor in concert with p53. We investigated the clinical significance of ARID1A protein expression in gastric cancer (GC), and examined its association with Epstein-Barr virus-associated (EBV) GC, mismatch repair (MMR) deficiency, and p53 alteration. We performed immunohistochemistry for ARID1A in 417 GC specimens using tissue microarray. EBV infection was examined using EBV-encoded small RNA in situ hybridization. Evaluation of MMR protein deficiency and p53 alteration was performed using immunohistochemistry, and microsatellite instability status was also assessed. Loss of ARID1A expression was observed in 21.1% of GC (88/417), but was not observed in gastric adenoma tissues or non-neoplastic gastric mucosa tissues. Loss of ARID1A showed positive correlations with advanced pTNM stage and tumor invasion (P=0.029 and 0.001, respectively). Overall survival was significantly influenced by the loss of ARID1A expression in wildtype p53 group (P=0.016, log-rank test). Moreover, ARID1A loss was significantly associated with EBV positivity, loss of MMR protein expression, and microsatellite instability high status (P=0.028,