通过测定胃癌患者血浆中细胞内游离DNA中PAX5、SEPT9和WIF-1基因启动子的甲基化情况，分析它们与胃癌疾病特征间的联系，并探讨三种基因启动子甲基化在筛查原发性胃癌中的协同检测功能。

利用巢氏甲基化特异性PCR技术（MDA-nMSP）检测2020年12月至2021年12月收治的81例胃癌患者（胃癌组）血液样本中的PAX5、SEPT9和WIF-1基因启动子的甲基化率。另选取同期年龄构成相似的39名健康者作为对照组，比较两组各基因甲基化率的差异，并通过受试者工作特征（ROC）曲线评估血浆甲基化PAX5、SEPT9和WIF-1对胃癌的预测价值。

胃癌组血浆PAX5、SEPT9及WIF-1甲基化率分别为38.3%、34.6%、46.9%，高于对照组的7.7%、10.3%、5.1%，差异均有统计学意义（χ²=12.123、7.956、20.683，均P<0.01）。PAX5和WIF-1基因启动子甲基化的发生与患者年龄相关（P<0.05），SEPT9基因启动子甲基化的发生与肿瘤大小相关（P<0.05）。作为诊断靶点，甲基化PAX5诊断胃癌的敏感度为38.27%，特异度为92.31%，曲线下面积（AUC）为0.653；SEPT9分别为34.57%、89.74%、0.622，WIF-1分别为46.91%、94.87%、0.709，三者联合诊断胃癌的敏感度、特异度分别为61.73%（95% CI：50.3%~72.3%）、84.62%（95% CI：69.5%~94.1%），AUC为0.732（95% CI：0.653~0.810）。

原发性胃癌患者血浆PAX5、SEPT9和WIF-1基因启动子甲基化率较高，三种甲基化基因联合诊断胃癌的特异度与单一基因诊断相似，但敏感度有较大提升，有望成为新的胃癌检测基因组合。

To determine the methylation of PAX5, SEPT9 and WIF-1 gene promoters in intracellular free DNA in the plasma of gastric cancer (GC) patients, and their relationship with the characteristics of GC, trying to explore the function of promoter methylation of the three genes in screening detection of primary GC.

The methylation rate of the PAX5, SEPT9, and WIF-1 gene promoters in blood samples from 81 GC patients (GC group) and 39 healthy controls (control group) were measured using the nest methylation-specific PCR technology (MDA-nMSP). The difference of gene methylation rates between the two groups was compared, and the predictive value of plasma methylated PAX5, SEPT9 and WIF-1 gene in GC were evaluated by the receiver operating characteristics (ROC) curve.

The methylation rates of PAX5, SEPT9 and WIF-1 in GC group were 38.3%, 34.6% and 46.9% respectively, while those in the control group were 7.7%, 10.3%, and 5.1% respectively. There were significant differences in methylation rates of the three genes between the two groups (χ²=12.123, 7.956, 20.683; all P<0.01). The occurrence of PAX5 and WIF-1gene promoter methylation were correlated with patients’ age (P<0.05), and the occurrence of SEPT9 gene promoter methylation was correlated with tumor size (P<0.05). As a diagnostic target of GC, the sensitivity, specificity and area under the curve (AUC) of methylated PAX5 were 38.27%, 92.31%, and 0.653 respectively; 34.57%, 89.74% and 0.622 respectively for SEPT9; 46.91%, 94.87%, and 0.709 respectively for WIF-1. The sensitivity and specificity of combined diagnosis for GC were 61.73% (95% CI: 50.3%-72.3%), 84.62% (95% CI: 69.5%-94.1%), and AUC value was 0.732 (95% CI: 0.653-0.810).

The methylation rates of PAX5, SEPT9 and WIF-1 gene promoters in plasma of patients with primary GC are high. When the combination of the three genes for diagnosis of GC, the specificity is similar to that by any single gene, but the sensitivity is greatly improved, which is expected to become a new gene combination for GC detection.