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

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

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.

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Biomarkers, Tumor / genetics*
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human