胃腺癌患者中 CDH11、EphA5 和 HS3ST2 基因的 CpG 岛甲基化分析。
CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients.
机构信息
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
J Gastrointest Cancer. 2020 Jun;51(2):579-583. doi: 10.1007/s12029-019-00290-1.
PURPOSE
Gastric cancer is an aggressive disease which is the fourth prevalent malignancy in the world. Beside the genetic factors, epigenetic alterations such as promoter CpG island hyper methylation are involved in the emergence of gastric cancer. Herein, we investigated the methylation status of CDH11, EphA5, and HS3ST2 genes in patients with and without gastric adenocarcinoma for the first time.
METHODS
In the study 40 paraffin-embedded tissue sections from gastric adenocarcinoma patients and 40 specimens from patients with functional dyspepsia were taken. DNA extraction was performed using a modified salting out method. Epizen DNA methylation kit was used to the bisulfite DNA conversion. The methylation status of CDH11, EphA5, and HS3ST2 genes were analyzed by methylation-specific PCR (MSP) technique.
RESULTS
Among the 80 specimens, 71 DNA samples were achieved (34 gastric adenocarcinoma patients and 37 control patients). The results showed that CDH11, EphA5, and HS3ST2 genes are methylated in 28 (82.45%), 19 (55.88%), and 26 (76.47%) of 34 DNA samples from gastric adenocarcinoma patients, respectively, whereas, these genes are methylated in 7 (18.91%), 9 (24.32%) and 7 (18.91%) of 37 samples from noncancerous patients, respectively. Statistical analyses using a chi-squared test showed that there is a statistically significant difference in methylation level of CDH11, EphA5, and HS3ST2 genes between gastric cancer and uncancerous patients (p < 0.05).
CONCLUSION
To the best of our knowledge, this is the first report on methylation of CDH11, EphA5, and HS3ST2 promoters' in gastric adenocarcinoma patients using MSP. Identification of novel cancer-related molecular mechanisms can be useful in detection of new treatment strategies.
目的
胃癌是一种侵袭性疾病，是世界上第四大常见恶性肿瘤。除了遗传因素外，表观遗传改变，如启动子 CpG 岛过度甲基化，也参与了胃癌的发生。在此，我们首次研究了 CDH11、EphA5 和 HS3ST2 基因在胃癌患者和非胃癌患者中的甲基化状态。
方法
本研究共收集了 40 例胃癌患者和 40 例功能性消化不良患者的石蜡包埋组织切片。采用改良盐析法提取 DNA。采用 Epizen DNA 甲基化试剂盒进行 bisulfite DNA 转化。采用甲基化特异性 PCR（MSP）技术分析 CDH11、EphA5 和 HS3ST2 基因的甲基化状态。
结果
在 80 例标本中，获得了 71 例 DNA 样本（34 例胃癌患者和 37 例对照患者）。结果显示，34 例胃癌患者的 DNA 样本中有 28 例（82.45%）、19 例（55.88%）和 26 例（76.47%）的 CDH11、EphA5 和 HS3ST2 基因发生甲基化，而非癌症患者的 37 例 DNA 样本中分别有 7 例（18.91%）、9 例（24.32%）和 7 例（18.91%）的 CDH11、EphA5 和 HS3ST2 基因发生甲基化。采用卡方检验进行统计学分析显示，胃癌患者和非胃癌患者的 CDH11、EphA5 和 HS3ST2 基因甲基化水平存在统计学差异（p<0.05）。
结论
据我们所知，这是首次采用 MSP 检测 CDH11、EphA5 和 HS3ST2 启动子在胃癌患者中的甲基化。鉴定新的与癌症相关的分子机制有助于发现新的治疗策略。
Zotero 插件