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FTO 的表达与胃癌的发生和预后有关。

FTO expression is associated with the occurrence of gastric cancer and prognosis.

机构信息

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, P.R. China.

Department of General Surgery, The Fourth Affiliated Hospital of Nantong University, Nantong University, Yancheng, Jiangsu, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2285-2292. doi: 10.3892/or.2017.5904. Epub 2017 Aug 14.

DOI:10.3892/or.2017.5904
PMID:28849183
Abstract

Fat mass and obesity associated (FTO) is a protein-coding gene. FTO gene is an obesity related gene, also known as the obesity gene. It has been reported previously that FTO is associated with a variety of malignant cancers, such as breast, thyroid and endometrial cancer. The aim of the present study was investigate the FTO expression of human gastric cancer and to investigate its clinical value. FTO expression was determined by immunohistochemical analysis with tissue microarrays in GC tissues and corresponding adjacent non-tumor tissues. Moreover, the results in protein and mRNA level were confirmed by the real-time PCR and western blot analysis. The relationship between the FTO expression and the pathological characteristics of GC patients was also explored. In addition, by using MTT, clone formation and transwell assays, we studied the effects of FTO expression on biological function of GC cells in vitro. The Kaplan-Meier method and the log-rank test were used to compare the overall survival rate between the FTO high-expression group and the low-expression group. We affirmed repeatedly upregulation of FTO expression in both protein and mRNA levels in GC tissues compared to corresponding adjacent non-tumor tissues. Immunohistochemistry by tissue microarray of FTO expression was remarkably increased in GC tissues (72 of 128, 56.3%) compared with adjacent non-tumor tissues (24 of 62, 38.7%). FTO expression level was closely related to low differentiation (P<0.001), lymph node metastasis (P=0.029). The expression of FTO was positively correlated with TNM stage (P<0.001). the Kaplan-Meier analysis showed that high FTO expression was significantly associated with poor prognosis in GC patients. Downregulation of FTO expression significantly inhibited the proliferation, migration and invasion of GC cell lines. On the contrary, overexpression of FTO promoted the proliferation, migration and invasion of GC cell lines. This study indicates that FTO expression may have an important role in promoting the occurrence of GC, and it may be an vital molecular marker in the diagnosis and prognosis of GC patients.

摘要

脂肪量和肥胖相关(FTO)是一种蛋白编码基因。FTO 基因是一种与肥胖相关的基因,也被称为肥胖基因。先前已有报道称,FTO 与多种恶性癌症有关,如乳腺癌、甲状腺癌和子宫内膜癌。本研究旨在探讨人类胃癌中 FTO 的表达及其临床意义。通过组织微阵列免疫组化分析检测 GC 组织及其相应的相邻非肿瘤组织中的 FTO 表达。此外,通过实时 PCR 和 Western blot 分析验证了蛋白和 mRNA 水平的结果。还探讨了 FTO 表达与 GC 患者病理特征之间的关系。另外,通过 MTT、克隆形成和 Transwell 测定,我们研究了 FTO 表达对 GC 细胞体外生物学功能的影响。采用 Kaplan-Meier 法和对数秩检验比较 FTO 高表达组和低表达组之间的总生存率。我们反复证实 FTO 在 GC 组织中的蛋白和 mRNA 水平均上调,与相应的相邻非肿瘤组织相比。通过组织微阵列的免疫组化分析,FTO 在 GC 组织中的表达明显高于相邻非肿瘤组织(72/128,56.3%比 24/62,38.7%)。FTO 表达水平与低分化(P<0.001)、淋巴结转移(P=0.029)密切相关。FTO 表达与 TNM 分期呈正相关(P<0.001)。Kaplan-Meier 分析表明,FTO 高表达与 GC 患者的预后不良显著相关。下调 FTO 表达可显著抑制 GC 细胞系的增殖、迁移和侵袭。相反,FTO 的过表达促进了 GC 细胞系的增殖、迁移和侵袭。本研究表明,FTO 表达可能在促进 GC 的发生中起重要作用,它可能是 GC 患者诊断和预后的重要分子标志物。

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