title: [Demethylation of the gamma-synuclein gene CpG island in colorectal cancer and its clinical significance].
abstract: OBJECTIVE
  To explore the relationship between gamma-synuclein gene expression and CpG island demethylation in colorectal cancer(CRC), and the relationship between the demethylation and clinicopathological factors of CRC.
  
  
  METHODS
  The expression of gamma-synuclein mRNA was examined in 30 pairs of tumor tissues and tumor-matched non-neoplastic adjacent tissues(NNAT) by RT-PCR. CRC cell lines including COLO205, LoVo, and SW480 were used and treated with a demethylating agent, 5-aza-2'-deoxycytidine(5-aza-C). Before and after the treatment, the expression of gamma-synuclein mRNA in the cells was determined by RT-PCR, and bisulfite sequencing PCR was also used to analyze methylation status of CpG island. The methylation status of gamma-synuclein was then examined in 67 CRC samples and 30 NNAT samples by nested methylation-specific PCR (NMSP) and real time methylation-specific PCR(real-time MSP). The relationship between the demethylation of gamma-synuclein in CRC and clinicopathological factors was analyzed.
  
  
  RESULTS
  The mean gamma-synuclein mRNA expression was 0.66+/-0.34 in CRC samples, which was much higher than 0.45+/-0.26 in NNAT samples(P=0.011). 5-aza-C could induce expression and demethylation of gamma-synuclein in COLO205, LoVo and SW480 cells. gamma-Synuclein gene was demethylated in 80.0%(24/30) of the CRC samples and 50.0%(15/30) of the NNAT samples. The demethylated status of gamma-synuclein was much higher in CRC samples than that in NNAT samples(P=0.030), and was significantly correlated with clinical stage, lymph node involvement, and distant metastasis of CRC(P<0.05).
  
  
  CONCLUSIONS
  The upregulation of gamma-synuclein expression in CRC is primarily attributed to the demethylation of CpG island, which may be used as a marker for prognosis.
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Minimally Invasive Surgery Center, Shanghai Institute of Digestive Surgery, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Yuan-fei
authors.initials: YF
authors.lastname: Peng
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.forename: Xue-hua
authors.initials: XH
authors.lastname: Chen
authors.forename: Bei-qin
authors.initials: BQ
authors.lastname: Yu
authors.forename: Jun-jun
authors.initials: JJ
authors.lastname: Ma
authors.forename: Ai-guo
authors.initials: AG
authors.lastname: Lu
authors.forename: Jian-wen
authors.initials: JW
authors.lastname: Li
authors.forename: Ming-liang
authors.initials: ML
authors.lastname: Wang
authors.forename: Bing-ya
authors.initials: BY
authors.lastname: Liu
authors.forename: Min-hua
authors.initials: MH
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051845:gamma-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051845:gamma-Synuclein