Epigenetic regulation of Wnt/β-catenin signal-associated genes in gastric neoplasia of the fundic gland (chief cell-predominant) type
Epigenetic regulation of Wnt/β-catenin signal-associated genes in gastric neoplasia of the fundic gland (chief cell-predominant) type
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DOI：
10.1111/pin.12509
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发表时间：
2017-03-01
影响因子：
2.2
通讯作者：
Watanabe, Sumio
中科院分区：
文献类型：
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作者：
Murakami, Takashi;Mitomi, Hiroyuki;Watanabe, Sumio
胃底腺（主细胞为主）型胃肿瘤（GNCCP）是胃肿瘤的一种罕见变异。这种肿瘤与Wnt/β-连环蛋白信号通路的激活有关;然而，这种激活的机制仍然未知。为了阐明Wnt/β-连环蛋白信号相关基因甲基化在GNCCP中的潜在作用，我们在26个GNCCP中对其相关基因（包括SFRP、APC、AXIN 2和MCC）进行了β-连环蛋白免疫染色和甲基化特异性聚合酶链反应（PCR）[ i.例如，胃底腺息肉（FGPs）27例，胃底腺息肉伴异型增生（FGP-Ds）12例，传统型胃腺癌（CGAs）27例。GNCCP和CGA的细胞核β-连环蛋白标记指数高于FGP和FGP-Ds。SFRPs、APC和AXIN 2在GNCCP和CGA中更频繁地甲基化（SFRP 1，88%/96%; SFRP 2，85%/93%; SFRP 4，73%/81%; APC，81%/81%; AXIN 2，81%/85%;分别）（分别为37%/50%; 41%/42%; 41%/58%; 37%/33%; 41%/50%）。在GNCCPs中，观察到细胞核b-连环蛋白表达与SFRP 1甲基化之间存在显著相关性。此外，高甲基化GNCCP的细胞核b-连环蛋白表达显著高于低甲基化肿瘤。总之，我们的研究结果表明，该途径的激活，介导的基因甲基化，可能与一些GNCCP案件的进展，类似于CGA。
Gastric neoplasia of the fundic gland (chief cell-predominant) type (GNCCP) is a rare variant of gastric tumor. This tumor is associated with activation of the Wnt/beta-catenin signaling pathway; however, the mechanisms underlying this activation remain unknown. To elucidate potential roles of Wnt/beta-catenin signal-associated gene methylation in GNCCP, we performed beta-catenin immunostaining and methylationspecific polymerase chain reaction (PCR) for their associated genes, including SFRPs, APC, AXIN2, and MCC, in 26 GNCCPs [ i. e., 11 intramucosal (GNCCP-Ms) and 15 submucosal tumors (GNCCP-SMs)], and compared with 27 fundic gland polyps (FGPs), 12 FGPs with dysplasia (FGP-Ds), 27 conventional gastric adenocarcinomas (CGAs). Nuclear beta-catenin labeling indices were higher in GNCCPs and CGAs than in FGPs and FGP-Ds. SFRPs, APC, and AXIN2 were more frequently methylated in GNCCPs and CGAs (SFRP1, 88%/96%; SFRP2, 85%/93%; SFRP4, 73%/81%; APC, 81%/81%; AXIN2, 81%/85%; respectively) than in FGPs and FGP-Ds (37%/50%; 41%/42%; 41%/58%; 37%/33%; 41%/50%; respectively). A significant correlation was seen between nuclear b-catenin expression and methylation of SFRP1 in GNCCPs. Furthermore, nuclear b-catenin expression was significantly frequent in high-methylated GNCCPs than in low-methylated tumors. In conclusion, our results suggest that activation of this pathway, mediated by gene methylation, may be associated with progression of some GNCCP cases, similar to CGAs.