Choi Boram, Han Tae-Su, Min Jimin, Hur Keun, Lee Sun-Min, Lee Hyuk-Joon, Kim Young-Joon, Yang Han-Kwang
a Cancer Research Institute , Seoul National University College of Medicine , Seoul , Korea.
b Division of Genetics , Cancer Research Institute, Kanazawa University , Kanazawa , Japan.
Biomarkers. 2017 Feb;22(1):35-44. doi: 10.1080/1354750X.2016.1201542. Epub 2016 Sep 22.
Gastric cancer (GC) is the fourth most common cause of cancer-related deaths worldwide.
To determine the mRNA-expression of the MAL, TMEM220, MMP28, IL-19 and HOPX genes and analyse the methylation statuses of MAL and TMEM220.
Gene-expression levels were analysed in 10 GC cell lines and 30 matched pairs of GC and normal mucosa (NM) gastric tissue specimens in real-time reverse-transcriptase polymerase chain reactions. Gene methylation was evaluated by bisulphite sequencing. Detailed gene-methylation patterns were confirmed by pyrosequencing analysis.
MAL, TMEM220, MMP28 and IL-19 were significantly down-regulated in GC cell lines and GC tissues compared to NM tissues. MAL and TMEM220 were highly methylated in GC tissues, and methylation inversely correlated with expression. MAL and TMEM220 expression were restored by treatment with 5-aza-2'-deoxycytidine. MAL and TMEM220 were specifically methylated and were down-regulated in human GC.
These loci may serve as novel methylation markers for patients with GC.
胃癌（GC）是全球癌症相关死亡的第四大常见原因。
确定MAL、TMEM220、MMP28、IL-19和HOPX基因的mRNA表达，并分析MAL和TMEM220的甲基化状态。
通过实时逆转录聚合酶链反应分析10种胃癌细胞系以及30对匹配的胃癌组织和正常胃黏膜（NM）组织标本中的基因表达水平。通过亚硫酸氢盐测序评估基因甲基化情况。通过焦磷酸测序分析确认详细的基因甲基化模式。
与NM组织相比，MAL、TMEM220、MMP28和IL-19在胃癌细胞系和胃癌组织中显著下调。MAL和TMEM220在胃癌组织中高度甲基化，且甲基化与表达呈负相关。用5-氮杂-2'-脱氧胞苷处理可恢复MAL和TMEM220的表达。MAL和TMEM220在人胃癌中特异性甲基化且表达下调。
这些基因座可能作为胃癌患者新的甲基化标志物。
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