Xue Wan-Jiang, Feng Ying, Wang Fei, Li Peng, Liu Yi-Fei, Guo Yi-Bing, Wang Zhi-Wei, Mao Qin-Sheng
Department of General Surgery, Nantong University Affiliated Hospital, 20 Xisi Street, Nantong, 226001, Jiangsu, China.
Department of Pathology, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
Tumour Biol. 2016 Aug;37(8):11249-57. doi: 10.1007/s13277-016-5001-6. Epub 2016 Mar 5.
The tumor-suppressing role of Ras-association domain family 10 (RASSF10) has been described in several types of cancers. Here, we evaluated the potential use of the hypermethylation status of the RASSF10 promoter in serum as a new diagnostic and prognostic tool in gastric cancer (GC). We used bisulfite sequencing polymerase chain reaction to examine RASSF10 methylation levels in serum and/or tumor samples from 82 GC, 45 chronic atrophic gastritis (CAG), and 50 healthy control patients. In the serum of GC patients, the median level of RASSF10 methylation was higher at 47.84 % than those in the serum of CAG and healthy control patients at 11.89 and 11.35 %, respectively. The median level of RASSF10 methylation in GC tumor tissue was similarly high at 62.70 %. Furthermore, RASSF10 methylation levels were highly correlated between paired serum and tumor samples from GC patients. We performed receiver-operating characteristic curve analyses to verify that serum RASSF10 methylation levels could effectively distinguish GC from control patients. Moreover, multivariate analyses showed that high serum RASSF10 methylation levels in GC patients were associated with large tumors, lymph node metastasis, and high carcinoembryonic antigen (CEA) levels. Survival analyses showed that GC patients with high serum RASSF10 methylation levels had shorter overall and disease-free survival after D2 lymphadenectomy than those with low levels. High serum RASSF10 methylation levels were also an independent predictor of tumor recurrence and GC patient survival. In conclusion, serum RASSF10 promoter methylation levels can serve as a valuable indicator for the diagnosis and prognosis of GC in the clinic.
Ras 关联结构域家族 10(RASSF10)的肿瘤抑制作用已在多种癌症中得到描述。在此,我们评估了血清中 RASSF10 启动子的高甲基化状态作为胃癌(GC)新的诊断和预后工具的潜在用途。我们使用亚硫酸氢盐测序聚合酶链反应来检测 82 例 GC 患者、45 例慢性萎缩性胃炎(CAG)患者和 50 例健康对照患者的血清和/或肿瘤样本中的 RASSF10 甲基化水平。在 GC 患者的血清中,RASSF10 甲基化的中位数水平较高,为 47.84%,分别高于 CAG 患者血清中的 11.89%和健康对照患者血清中的 11.35%。GC 肿瘤组织中 RASSF10 甲基化的中位数水平同样较高,为 62.70%。此外,GC 患者配对的血清和肿瘤样本之间的 RASSF10 甲基化水平高度相关。我们进行了受试者工作特征曲线分析,以验证血清 RASSF10 甲基化水平可有效区分 GC 患者与对照患者。此外,多变量分析表明,GC 患者血清中高 RASSF10 甲基化水平与肿瘤体积大、淋巴结转移和癌胚抗原(CEA)水平高有关。生存分析表明,血清 RASSF10 甲基化水平高的 GC 患者在 D2 淋巴结清扫术后的总生存期和无病生存期比水平低的患者短。血清 RASSF10 高甲基化水平也是肿瘤复发和 GC 患者生存的独立预测指标。总之,血清 RASSF10 启动子甲基化水平可作为临床上 GC 诊断和预后的有价值指标。