Hypermethylation and prognostic implication of Syk gene in human colorectal cancer

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• 作者：Zuli Yang (1)
  Lijun Huo (2)
  Hao Chen (1)
  Beibei Ni (3)
  Jun Xiang (1)
  Liang Kang (4)
  Lei Wang (4)
  Junsheng Peng (1)
  Yunfei Yuan (5)
  Jianping Wang (4)
  
• 关键词：Colorectal cancer ; Spleen tyrosine kinase (Syk) ; Tumor suppressor gene ; DNA methylation/epigenetics
• 刊名：Medical Oncology
• 出版年：2013
• 出版时间：June 2013
• 年：2013
• 卷：30
• 期：2
• 全文大小：440KB
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• 作者单位：Zuli Yang (1)
  Lijun Huo (2)
  Hao Chen (1)
  Beibei Ni (3)
  Jun Xiang (1)
  Liang Kang (4)
  Lei Wang (4)
  Junsheng Peng (1)
  Yunfei Yuan (5)
  Jianping Wang (4)
  
  1. Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, Guangzhou, People’s Republic of China
  2. Department of Ophthalmology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, People’s Republic of China
  3. Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, People’s Republic of China
  4. Department of Colon and Rectum Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People’s Republic of China
  5. Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China
  

文摘

The study was aimed to investigate the relationship between hypermethylation of Syk gene and clinicopathological characteristics and long-term outcomes in colorectal cancer. The effect of Syk on cell proliferation and invasion ability was also assessed. Methylation and expression status of Syk were explored in CRC tissues and cell lines by MSP, qRT-PCR and western blot assay. The effects of Syk overexpression on tumorigenesis were studied by in vitro assay. The correlation between Syk methylation and clinical relevance in CRC patients was also analyzed. Syk methylation was found 48.6?% in CRC tissue samples and 57.1?% in cell lines, respectively. The loss of Syk expression could be restored by demethylation agent. Overexpression of Syk in CRC cell inhibited cell proliferation (p?<?0.01) and invasion (p?<?0.01). The methylation of Syk was significantly associated with histological grade (p?=?0.002), lymph node status (p?<?0.001) and TNM stage (p?<?0.001). Five-year overall survival in methylated Syk group was significantly lower than that in unmethylated Syk group (59 vs. 80?%, p?<?0.001). Multivariate analysis demonstrated that Syk methylation was an independent prognostic factor for overall survival. Syk is identified as a potential tumor suppressor in CRC progression. Syk methylation is correlated with poor overall survival, which acts as an independent prognostic indicator of CRC.