Aberrant expression of AID and AID activators of NF-κB and PAX5 is irrelevant to EBV-associated gastric cancers, but is associated with carcinogenesis in certain EBV-non-associated gastric cancers.
Aberrant expression of AID and AID activators of NF-κB and PAX5 is irrelevant to EBV-associated gastric cancers, but is associated with carcinogenesis in certain EBV-non-associated gastric cancers.
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DOI：
10.3892/ol.2017.5978
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发表时间：
2017-06
期刊：
影响因子：
2.9
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
作者：
Mohri T;Nagata K;Kuwamoto S;Matsushita M;Sugihara H;Kato M;Horie Y;Murakami I;Hayashi K
EB病毒相关胃癌（EBVaGC）是胃癌的一个独特亚型，其临床病理特征包括淋巴上皮瘤样组织学。激活诱导的胞苷脱氨酶（AID）作为一种基因组调节因子通过病原体相关核因子κB（NF-κB）信号传导在幽门螺杆菌相关胃癌中的异常表达得到证实。为了阐明AID的表达是否与EBVaGC的癌变有关，我们对15例伴有淋巴样间质（GCLS）的胃癌和其他类型的胃癌进行了免疫组化检测，分析了AID和AID调节因子在EBVaGC和EBV非相关胃癌（GC）中的表达。与EBV非相关性胃癌（7/19，12/19和11/19）相比，EBV VaGC（0/11，1/11和1/11）中AID，NF-κB和配对盒5（PAX 5）的异常表达显著降低（P分别为0.025，0.005和0.01）;然而，未发现c-MyB原癌基因表达的显著差异。EBV相关性GCLS中AID的表达（0/10）也低于非EBV相关性GCLS（3/5）。GCLS组NF-κB和PAX 5的表达（1/15和2/15）明显低于无LS组（12/15和10/15）（P分别<0.001和P=0.003）。在EBVaGC中观察到的AID表达降低与EBVaGC中报告的高甲基化和罕见体细胞基因突变的分子特征一致。只有PAX 5与静脉侵犯显著相关（P=0.022）。本研究的结果表明，病原体诱导的AID的表达可能是无关的EBVaGC的致癌作用，而它有助于某些类型的EBV非相关的GC的致癌作用。
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC. Aberrant expression of AID, NF-κB and paired box 5 (PAX5) were significantly decreased in EBVaGC (0/11, 1/11 and 1/11) compared with in EBV-non-associated GC (7/19, 12/19 and 11/19) (P=0.025, 0.005 and 0.01, respectively); however, no significant difference in c-Myb proto-oncogene expression was identified. AID expression was also decreased in EBV-associated GCLS (0/10) compared with in EBV-non-associated GCLS (3/5). Unexpectedly, decreased expression of NF-κB and PAX5 was observed in GCLS (1/15 and 2/15) compared with in GC without LS (12/15 and 10/15) (P<0.001 and P=0.003, respectively). Decreased AID expression observed in EBVaGC is consistent with the reported molecular characterization of hypermethylation and rare somatic gene mutation in EBVaGC. Only PAX5 was identified to be significantly associated with venous invasion (P=0.022). The results of the present study suggest that pathogen-induced AID expression may be irrelevant to carcinogenesis of EBVaGC, whereas it contributes to carcinogenesis in certain types of EBV-non-associated GC.