Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer.

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer.
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G蛋白γ7(GNG7)在食道癌中的表达降低的临床意义。

DOI:
10.1038/sj.bjc.6604124
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发表时间:
2008-01-29
影响因子:
8.8
通讯作者:
Mori, M.
Mori, M.
中科院分区:
医学1区
文献类型:
--
作者:
Ohta, M.;Mimori, K.;Fukuyoshi, Y.;Kita, Y.;Motoyama, K.;Yamashita, K.;Ishii, H.;Inoue, H.;Mori, M.

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我们之前克隆了人类G蛋白γ 7(GNG 7),并证明它在胃肠道癌症中下调。GNG7在食管癌中表达的意义尚不清楚。采用TaqMan实时荧光定量PCR方法检测55例食管癌组织中GNG7的表达,并分析其临床意义。此外,在基因组和表观遗传水平的实验室研究中分析了GNG7转染的食管癌细胞。27例GNG7低表达患者的生存率明显低于28例高表达患者(P<0.05)。无论是在体内还是体外,GNG7低表达的肿瘤均比GNG7高表达的肿瘤侵袭更深(P<0.05)。8个肿瘤保留了GNG7表达,它们没有显示启动子高甲基化或杂合性缺失(洛)。在38例GNG 7抑制的肿瘤中,22例(57%)显示洛缺失或启动子高甲基化。此外,在食管癌细胞系中,GNG7表达与miR328的存在显著相关,这表明该microRNA可能是GNG7表达的调节因子。GNG7抑制代表了食管癌病例中的新预后指标。GNG7可能受到洛缺失和启动子高甲基化或microRNA的抑制。
We previously cloned human G protein gamma 7 (GNG7) and demonstrated that it was downregulated in gastrointestinal cancer. The significance of GNG7 expression in oesophageal cancer is unknown. TaqMan quantitative real-time PCR was performed to determine the clinical significance of GNG7 expression in 55 cases of oesophageal cancer. Furthermore, GNG7-transfected oesophageal cancer cells were analysed in laboratory studies at genomic and epigenetic levels. Twenty-seven patients with low GNG7 expression showed significantly poorer survival than did 28 patients with high expression (P<0.05). Tumours with low GNG7 expression invaded deeper than those with high GNG7 expression (P<0.05), both in vivo and in vitro. Eight tumours retained GNG7 expression, and they did not show either promoter hypermethylation or loss of heterozygosity (LOH). In 38 tumours with GNG7 suppression, 22 (57%) showed either LOH or promoter hypermethylation. In addition, GNG7 expression was significantly associated with the presence of miR328 in oesophageal cancer cell lines, which suggests that this microRNA might be a regulator of GNG7 expression. GNG7 suppression represents a new prognostic indicator in cases of oesophageal cancer. GNG7 might be suppressed by LOH and promoter hypermethylation or by microRNA.
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