title: Decreased 5-hydroxymethylcytosine (5-hmC) is an independent poor prognostic factor in gastric cancer patients.
abstract: DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is involved in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Increasing evidence suggests that large-scale loss of 5-hmC is an epigenetic hallmark of several human cancers. However, the value of 5-hmC in diagnosis and prognosis of human cancers, including gastric cancer (GC), remains largely unknown. The aim of this study is to determine 5-hmC levels in GCs and explore its association with clinicopathological characteristics and clinical outcome of GC patients. Using immunohistochemistry (IHC) and dot-blot assays, we demonstrated that 5-hmC was dramatically decreased in GCs compared with matched normal tissues. We also found a strong link between decreased 5-hmC and the reduction of TET1 gene expression, but not TET2 or 3, suggesting that decreased TET1 expression might be one of the mechanisms underlying 5-hmC loss in GCs. Wilcoxon tests showed that 5-hmC content was significantly associated with most of clinicopathological characteristics, such as tumor size (P = 0.016), Bormman type (P < 0.0001), tumor invasion (P = 0.001), TNM stage (P < 0.0001), the number of lymph nodes metastasis (P = 0.002), and survival status (P < 0.0001). It is noteworthy that decreased 5-hmC was significantly associated with poor survival of GC patients. Collectively, our findings indicate that decreased 5-hmC may be crucial to the clinical pathology of GC and is a strong and independent poor prognostic factor in GCs.
authors: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors: Qi
authors: Q
authors: Yang
authors: Kexia
authors: K
authors: Wu
authors: Meiju
authors: M
authors: Ji
authors: Weilin
authors: W
authors: Jin
authors: Nongyue
authors: N
authors: He
authors: Bingyin
authors: B
authors: Shi
authors: Peng
authors: P
authors: Hou
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002681:China / Q000453:epidemiology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine