Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Gastrointestinal and liver diseases research center (GLDRC), Guilan University of Medical Sciences, Rasht, Iran.
Pathol Oncol Res. 2019 Jul;25(3):1215-1222. doi: 10.1007/s12253-019-00594-4. Epub 2019 Jan 26.
Gastric cancer is among the commonplace causes of cancer death worldwide. Sonic hedgehog (Shh) signaling is an important pathway which may be dysregulated in many cancers.CDX1/2, and KLF5are key transcription factors involved in Shh pathway and cancer stem cells. The aim of this study was to investigate the expression and epigenetic alterations of these genes in gastric cancer patients. DNA methylation's modifications of CDX1, KLF5 and CDX2 genes alongside with the expressions of these genes in gastric cancer tissues and their non-tumoral counterparts (margin tissues) were analyzed using methylation specific sequencing, and Real time PCR Taq man assays, respectively. The expression of CDX1 (P = 0.002) and KLF5 (P = 0.010) were decreased significantly, but it was considerably increased for CDX2 (P = 0.001). Relatively, the results for the regulatory region methylation status of each CpG site had shown a notable fluctuation in these genes with no significant difference in most places. The creation of metastatic lymph nodes in patients was significantly associated with increased expression of CDX2 gene. The modifications of these genes expression can be considered as a cancer biomarker in future studies. Methylation of the investigated genes is not the main mechanism of gastric cancer development.
胃癌是全球常见的癌症死因之一。Sonic hedgehog（Shh）信号通路是许多癌症中可能失调的重要途径。CDX1/2 和 KLF5 是参与 Shh 通路和癌症干细胞的关键转录因子。本研究旨在探讨这些基因在胃癌患者中的表达和表观遗传改变。使用甲基化特异性测序和实时 PCR Taqman 测定法分别分析了 CDX1、KLF5 和 CDX2 基因的 DNA 甲基化修饰以及这些基因在胃癌组织及其非肿瘤对应物（边缘组织）中的表达。CDX1（P=0.002）和 KLF5（P=0.010）的表达显著降低，但 CDX2 的表达显著增加（P=0.001）。相对而言，每个 CpG 位点的调控区甲基化状态的结果表明，这些基因在大多数地方的波动没有显著差异。患者中转移性淋巴结的形成与 CDX2 基因表达的增加显著相关。这些基因表达的修饰可以在未来的研究中被视为癌症生物标志物。研究基因的甲基化不是胃癌发展的主要机制。
