Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350122, China.
Exp Mol Pathol. 2020 Oct;116:104493. doi: 10.1016/j.yexmp.2020.104493. Epub 2020 Jul 11.
Previous study has shown LEPR is a candidate gene of prediction and treatment of gastric cancer (GC). The purpose of this study was to test whether LEPR methylation could predict the risk of GC.
Tumor tissues and 5-cm adjacent non-tumor tissues from 117 newly diagnosed and untreated GC patients were collected for the current methylation study. LEPR methylation levels were determined by quantitative methylation specific PCR (qMSP), and the methylation level of LEPR was described by the percentage of methylated reference (PMR).
Our results showed that LEPR methylation levels were significantly lower in tumor tissues than those in adjacent non-tumor tissues (median PMR: 36.64% vs. 50.29%, P = 1E-4). In addition, LEPR methylation levels were found to be significantly associated with platelet (r = -0.198, P = .037). Further subgroup analysis showed that the association of LEPR promoter hypomethylation with GC was specific to males (males: P = 7E-5; females: P = .500). Notably, significant hypomethylation of LEPR promoter was found only in GC patients without recurrence (P = .002) but not in GC patients with recurrence (P = .146). The AUC of LEPR hypomethylation for identification of GC risk was 0.649 with a sensitivity of 67.5% and a specificity of 63.2%. In addition, the AUC of LEPR hypomethylation in males was 0.685 with a sensitivity of 68.4% and a specificity of 69.6%.
LEPR hypomethylation can be used to predict the risk of GC in males. And it might also have the potential to predict the recurrence in GC patients.
先前的研究表明 LEPR 是预测和治疗胃癌(GC)的候选基因。本研究旨在检验 LEPR 甲基化是否可预测 GC 的发病风险。
收集了 117 例新诊断且未经治疗的 GC 患者的肿瘤组织和 5cm 癌旁非肿瘤组织,用于当前的甲基化研究。采用实时甲基化特异性 PCR(qMSP)定量检测 LEPR 甲基化水平,采用甲基化参考的百分比(PMR)来描述 LEPR 的甲基化水平。
研究结果显示,肿瘤组织中 LEPR 甲基化水平显著低于癌旁非肿瘤组织(中位数 PMR:36.64%比 50.29%,P=1E-4)。此外,LEPR 甲基化水平与血小板计数呈显著负相关(r=-0.198,P=0.037)。进一步的亚组分析显示,LEPR 启动子低甲基化与 GC 的相关性仅存在于男性(男性:P=7E-5;女性:P=0.500)。值得注意的是,仅在无复发的 GC 患者中观察到 LEPR 启动子显著低甲基化(P=0.002),而在复发的 GC 患者中则未观察到(P=0.146)。LEPR 低甲基化用于识别 GC 风险的 AUC 为 0.649,灵敏度为 67.5%,特异性为 63.2%。此外,男性中 LEPR 低甲基化的 AUC 为 0.685,灵敏度为 68.4%,特异性为 69.6%。
LEPR 低甲基化可用于预测男性 GC 的发病风险,并且可能具有预测 GC 患者复发的潜力。