摘要
目的探讨原钙黏附蛋白17(PCDH17)基因甲基化与胃癌的关系及其在胃癌诊断中的价值。方法采用荧光定量甲基化特异性PCR法分析正常胃黏膜上皮细胞株GES-1和胃癌细胞株MGC-803、AGS和SGC-7901,120对胃癌组织及对应癌旁正常组织,120例胃癌患者血浆样本和120例健康体检者血浆样本中PCDH17基因甲基化水平;并分析胃癌组织中PCDH17基因甲基化水平与临床病理特征的关系。比较胃癌组织和血浆样本中PCDH17基因甲基化的诊断效能,评估PCDH17基因甲基化在胃癌诊断中的价值。结果 3株胃癌细胞PCDH17基因甲基化水平均明显高于正常胃黏膜上皮细胞,差异均有统计学意义(均P<0.01)。胃癌组织中PCDH17基因甲基化水平明显高于对应癌旁正常组织,差异有统计学意义(P<0.01)。胃癌组织中PCDH17基因甲基化水平与糖类抗原19-9表达情况、淋巴管侵犯、神经侵犯、淋巴结转移和Stage分期均有关(均P<0.05)。胃癌患者血浆样本中PCDH17基因甲基化水平明显高于健康体检者,差异有统计学意义(P<0.01)。在胃癌组织中,PCDH17基因甲基化水平用于诊断胃癌的AUC为0.73,灵敏度为0.58,特异度为0.80。在血浆样本中,PCDH17基因甲基化水平用于诊断胃癌的AUC为0.77,灵敏度为0.63,特异度为0.83。结论 PCDH17基因甲基化在胃癌发生、发展过程中发挥重要作用。PCDH17基因甲基化水平可作为胃癌的早期无创筛查的生物标志物。
Objective To assess the value of protocadherin 17(PCDH17) hyrermethylation in diagnosis of gastric cancer (GC). Methods The quantitative methylation-specific polymerase chain reaction was applied to assess the methylation level of PCDH17 in GC cell lines MGC-803, AGS, SGC-7901 and normal gastric epithelial cell line GES-1;120 GC and corresponding normal gastric tissue samples;as well as in plasma samples from 120 patients with GC and 120 healthy subjects. The relationship between PCDH17 hyrermethylation and clinicopathologic features of GC patients was evaluated. The diagnostic value of PCDH17 methylation in tissue samples and blood samples of GC patients was analyzed with receiver operating characteristic(ROC) curve. Results The methylation level of PCDH17 was significantly higher in three GC cell lines compared with normal gastric mucosal epithelial cells(all P<0.01). The methylation level of PCDH17 was statistically higher in GC tissues compared with normal gastric tissues(P<0.01). Hypermethylated PCDH17 was correlated with CA199 expression, lymphatic invasion, lymph node metastasis, nerve invasion, and clinical stage of GC(all P<0.05). The methylation level of PCDH17 was also significantly higher in GC blood sample compared with normal controls(P<0.01). The area under the ROC curve (AUC) of PCDH17 methylation was 0.73;and the sensitivity and specificity for distinguishing GC from normal tissue were 0.58 and 0.80, respectively. While, the AUC of plasma methylated PCDH17 was 0.77;and the sensitivity and specificity for diagnosis of GC were 0.63 and 0.83, respectively. Conclusion PCDH17 hypermethylation may be involved in the progress of GC, and might be served as a non-invasive biomarker for diagnosis of GC.
作者
朱春霞
周善学
胡桂梅
叶国良
ZHU Chunxia;ZHOU Shanxue;HU Guimei(Department of Gastroenterology, the Affiliated Hospital of Medicine School of Ningbo University, Ningbo 315020, China)
出处
《浙江医学》
CAS
2019年第9期876-880,共5页
Zhejiang Medical Journal
基金
宁波市自然科学基金项目(2017A610150)
作者简介
通信作者:叶国良,E-mail:ndfyygl@126.com.