Department of Oncology, the Second Hospital of Dalian Medical University.
Department of Obstetrics and Gynecology, the First Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China.
Medicine (Baltimore). 2021 Jan 29;100(4):e23788. doi: 10.1097/MD.0000000000023788.
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related mortality globally. Abnormal DNA methylation is closely related to gastric cancer. The purpose of the study was to investigate the methylation of the SYNE1 and MAGI2 gene promoter and its relationship with the clinical-pathological factors, chemotherapy efficacy, and survival, thus providing a new biomarker for the prognosis and chemotherapy efficacy in gastric cancer.The methylation status of SYNE1 and MAGI2 in gastric cancer and adjacent tissues was detected by MSP method in 70 cases of advanced gastric cancer paraffin specimens.The methylation rate of the SYNE1 and MAGI2 gene promoter region was higher in gastric cancer tissues compared with adjacent tissues. The methylation status of SYNE1 was associated with the age at diagnosis and the size of the primary tumors, but no clinical or pathological factors have been found to be related with the methylation status of MAGI2 promoter. A high level of SYNE1 promoter methylation was associated with poorer chemotherapy efficacy in recurrent patients with gastric cancer. Thirty-three percent of the 70 patients exhibited highly methylated MAGI2; in this group, the median progression-free survival time was 4.1 months, shorter than those with negative methylated MAGI2 whose PFS was 5.1 months.MAGI2 is more methylated in gastric cancer than in adjacent tissues suggesting that hypermethylation changes in MAGI2 may be one of the mechanisms of tumorigenesis in gastric cancer. The methylation status of the SYNE1 and MAGI2 promoter regions may affect the chemotherapy efficacy of advanced gastric cancer. The prognosis of MAGI2-negative patients was better than that of positive ones, suggesting that MAGI2 may be an independent prognostic factor for PFS in patients with advanced gastric cancer.
胃癌是全球第五大常见癌症,也是癌症相关死亡的第三大主要原因。异常的 DNA 甲基化与胃癌密切相关。本研究旨在探讨 SYNE1 和 MAGI2 基因启动子的甲基化及其与临床病理因素、化疗疗效和生存的关系,为胃癌的预后和化疗疗效提供新的生物标志物。
采用 MSP 法检测 70 例晚期胃癌石蜡标本中 SYNE1 和 MAGI2 基因启动子区的甲基化状态。胃癌组织中 SYNE1 和 MAGI2 基因启动子区的甲基化率高于相邻组织。SYNE1 的甲基化状态与诊断时的年龄和原发肿瘤的大小有关,但尚未发现与 MAGI2 启动子甲基化状态相关的临床或病理因素。SYNE1 启动子高甲基化与复发性胃癌患者化疗疗效较差有关。70 例患者中有 33%表现出 MAGI2 高甲基化;在这组患者中,中位无进展生存期为 4.1 个月,短于 MAGI2 阴性甲基化患者的 5.1 个月。
MAGI2 在胃癌中的甲基化程度高于相邻组织,提示 MAGI2 中异常高甲基化的改变可能是胃癌发生的机制之一。SYNE1 和 MAGI2 启动子区的甲基化状态可能影响晚期胃癌的化疗疗效。MAGI2 阴性患者的预后优于阳性患者,提示 MAGI2 可能是晚期胃癌患者无进展生存期的独立预后因素。