Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
J Biomed Nanotechnol. 2013 Sep;9(9):1607-16. doi: 10.1166/jbn.2013.1713.
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.
胞嘧啶 5 位的 DNA 甲基化（5-mC）是一种关键的表观遗传标记，参与多种生物学和病理学过程。5-mC 可以通过 ten-eleven 易位（TET）家族的 DNA 羟化酶转化为 5-羟甲基胞嘧啶（5-hmC）。越来越多的证据表明，5-hmC 的大量丢失是几种人类癌症的表观遗传标志。然而，5-hmC 在人类癌症（包括胃癌（GC））的诊断和预后中的价值在很大程度上仍然未知。本研究旨在确定 GC 中 5-hmC 的水平，并探讨其与 GC 患者的临床病理特征和临床结局的关系。通过免疫组化（IHC）和斑点印迹分析，我们证实与匹配的正常组织相比，GC 中 5-hmC 显著降低。我们还发现，5-hmC 减少与 TET1 基因表达的减少密切相关，但与 TET2 或 TET3 无关，这表明 TET1 表达的降低可能是 GC 中 5-hmC 丢失的机制之一。Wilcoxon 检验显示，5-hmC 含量与大多数临床病理特征显著相关，如肿瘤大小（P = 0.016）、Bormman 型（P < 0.0001）、肿瘤侵袭（P = 0.001）、TNM 分期（P < 0.0001）、淋巴结转移数（P = 0.002）和生存状态（P < 0.0001）。值得注意的是，5-hmC 减少与 GC 患者的不良生存显著相关。综上所述，我们的研究结果表明，5-hmC 的减少可能对 GC 的临床病理学至关重要，并且是 GC 中一个强有力的独立不良预后因素。
