SOX9 expression and its methylation status in gastric cancer
SOX9 expression and its methylation status in gastric cancer
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DOI：
10.1007/s00428-012-1201-7
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发表时间：
2012-03-01
期刊：
影响因子：
3.5
通讯作者：
Fukayama, Masashi
中科院分区：
文献类型：
--
作者：
Sun, Minhua;Uozaki, Hiroshi;Fukayama, Masashi
SOX 9是SOX（Sry相关高迁移率族（HMG）盒）家族的成员，是多种细胞谱系发育和分化所必需的。为了阐明SOX 9在胃癌中的意义，我们检测了SOX 9的免疫组化表达和SOX 9的CpG岛甲基化状态，并与包括总生存期在内的临床病理因素进行比较。在382个GC肿瘤中检测了SOX 9的表达，并在121个GC肿瘤中检测了其甲基化状态。还检查了6个GC细胞系、它们的EB病毒（EBV）感染的细胞系和2个EBV相关的GC细胞系中的SOX 9表达及其甲基化状态。从非肿瘤性粘膜到早期癌，SOX 9表达增加。212例（56%）患者中观察到SOX 9的高表达。SOX9表达与肿瘤分期、血管浸润、淋巴结转移和EBV感染呈负相关。121例胃癌中有58例（48%）胃癌启动子甲基化，甲基化状态与低表达相关。其表达及甲基化状态与预后无关。6个细胞系中有3个通过EBV感染增加了甲基化，并降低了SOX 9表达。S0X9的上调与GC发展相关。启动子甲基化下调与胃癌进展和EBV感染有关。SOX 9与胃癌的发生和EBV相关的胃癌的发生密切相关。
SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family and is required for the development and differentiation of multiple cell lineages. To clarify the significance of SOX9 in gastric carcinoma (GC), immunohistochemical expression of SOX9 and the CpG island methylation status of SOX9 were evaluated and compared with clinicopathological factors including overall survival. SOX9 expression was immunohistochemically evaluated in 382 GC tumors and the methylation status was examined in 121 GC tumors. SOX9 expression and its methylation status in six GC cell lines, their Epstein-Barr virus (EBV)-infected cell lines, and two EBV-associated GC cell lines was also examined. The SOX9 expression increased from non-neoplastic mucosa to early cancer. High expression of SOX9 was seen in 212 cases (56%). SOX9 expression was inversely related to advanced tumor stage, vessel infiltration, nodal metastasis, and EBV infection. Fifty-eight (48%) of 121 GC tumors had a methylated promoter in GC and the methylated status was related to low expression. The expression and methylation status were not related to prognosis. Three of six cell lines had increased methylation through EBV infection and decreased SOX9 expression. Upregulation of SOX9 is related to GC development. Downregulation by promoter methylation is related to GC progression and EBV infection. SOX9 is closely related to GC carcinogenesis and EBV-associated GC carcinogenesis.