title: Hypermethylation and prognostic implication of Syk gene in human colorectal cancer.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zuli
authors.initials: Z
authors.lastname: Yang
authors.forename: Lijun
authors.initials: L
authors.lastname: Huo
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Beibei
authors.initials: B
authors.lastname: Ni
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.forename: Liang
authors.initials: L
authors.lastname: Kang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Junsheng
authors.initials: J
authors.lastname: Peng
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase