title: Correlation of epigenetic aberrance with STAT3 signaling pathway in gastric carcinogenesis.
abstract: BACKGROUND
  It has been suggested that STAT3 signaling plays important roles in regulating epigenetic aberrance during tumorigenesis, especially in the expression of certain key epigenetic enzymes such as DNMTs, HDACs, and HMTs. However, there has been no report on the relationship of STAT3 signaling and epigenetic aberrance in gastrocarcinogenesis.
  
  
  OBJECTIVE
  The purpose of this study was to explore the interrelationship of STAT3 signaling pathway and epigenetic aberrance in gastrocarcinogenesis.
  
  
  METHODS
  Immunohistochemistry was utilized to examine the protein expressions of pSTAT3, DNMT1, HDAC1, and EZH2 in 153 tissue specimens, including 20 of normal gastric epithelium tissue, 21 of intestinal metaplasia (IM), 24 of dysplasia (DYS), 23 of early gastric cancer (EGC) and 65 of advanced gastric cancer (AGC), and then analyze their possible relationship with clinicopathological factors.
  
  
  RESULTS
  We found that the four protein expressions were obviously enhanced following the malignant process of gastric carcinogenesis. Pearson correlation analysis of all the pathological groups showed that expression of pSTAT3 was highly associated with DNMT1, but not with HADC1 and EZH2. However, significant correlations were detected among the expression of DNMT1, HDAC1, and EZH2. Further analysis of each pathological group demonstrated that pSTAT3's expression was dramatically related with DNTM1 in the IM (P = 0.021) and EGC groups (P = 0.013) and correlated with EZH2 in the DYS group (P = 0.020). Furthermore, pSTAT3's expression was associated with T staging (P = 0.015) in the AGC group, whereas DNMT1 was associated with gender (P = 0.021), HDAC1 with Lauren classification (P = 0.007), and EZH2 with T staging (P = 0.003) and lymphatic staging (P = 0.038).
  
  
  CONCLUSIONS
  The STAT3 signaling pathway may correlate with epigenetic aberrance during gastrocarcinogenesis.
authors.affiliation: Department of Gastroenterology, The Drum Tower Hospital Affiliated to Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, People's Republic of China.
authors.forename: Fuli
authors.initials: F
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Lv
authors.forename: Yinxin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000209:etiology* / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D005260:Female; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1