胃癌原发灶和转移淋巴结中酪氨酸磷酸酶受体基因甲基化的差异

Methylation of PTPRG gene and its regulation in gastric cancer

目的研究酪氨酸磷酸酶受体（PTPRG）基因在胃癌原发灶和转移淋巴结中的甲基化差异，以及甲基化抑制剂5-氮脱氧胞苷对于胃癌细胞系甲基化水平的调控功能，进一步阐述胃癌转移的表遗传学机制。方法应用甲基化特异性PCR（MSP）和逆转录聚合酶链反应（RT-PCR）方法，检测36例胃癌原发灶和转移淋巴结之间PTPRG基因的甲基化差异；检测胃癌细胞系在甲基化抑制剂干预前后PTPRG基因的甲基化及表达调控情况。结果胃癌原发灶和转移淋巴结PTPRG基因甲基化率分别为25．0％和52．8％，两者PTPRG mRNA表达率分别为50．0％和25．0％，差异均有统计学意义（P〈0．05）。胃癌细胞系经甲基化抑制剂干预后，PTPRG基因发生脱甲基化，PTPRG mRNA恢复表达。结论PTPRG基因在胃癌原发灶和转移淋巴结之间存在明显的甲基化差异。甲基化抑制剂5-氮脱氧胞苷可以降低胃癌细胞系的甲基化水平，恢复PTPRG基因的表达。

Objective To investigate the difference in methylation of PTPRG gene between gastric primary cancer and its lymph node metastases, and its regulation by 5-Aza-2＇-deoxycytidin in a gastric cancer cell line SGC7901. Methods Methylation-specific polymerase chain reaction （MSP） and RT-PCR were applied to identify the difference between gastric primary cancer and lymph node metastases and assess the changes of methylation in gastric cancer cell line SGC7901 treated by 5-Aza-2＇-deoxycytidin. Results There were significant differences of PTPRG gene methylation and PTPRG mRNA expression between gastric primary cancer and lymph node metastases： a linear regression analysis revealed a significant association between the quantity of metastatic lymph nodes and their methylation rate. A statisticd relationship between methylation of PTPRG gene and loss of PTPRG mRNA expression was detected. PTPRG gene methylation in the gastric cancer cell line changed into negative and PTPRG mRNA expression in the cell line was recovered after 5-Aza-2＇-deoxycytidin treatment. Conclusion There is a difference of PTPRG gene methylation in gastric primary cancer and metastatic lymph nodes. 5-Aza-2＇-deoxycytidin, an inhibitor of DNA methylation, can recovery the expression of PTPRG gene.