Wen Jinfeng, Zheng Tuo, Hu Kefeng, Zhu Chunxia, Guo Lihua, Ye Guoliang
Department of Gastroenterology, The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315020, People's Republic of China.
Department of Gastroenterology, Ningbo No.1 Hospital, Ningbo, Zhejiang 315000, People's Republic of China.
Oncotarget. 2017 Sep 8;8(44):77783-77793. doi: 10.18632/oncotarget.20782. eCollection 2017 Sep 29.
Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A (), E-cadherin (), runt-related transcription factor 3 (), human mutL homolog 1 (), RAS association domain family protein 1A (), cyclin-dependent kinase inhibitor 2B (), adenomatous polyposis coli (), Glutathione S-transferase P1 (), TP53 dependent G2 arrest mediator candidate (), and O6-methylguanine-DNAmethyl-transferase () promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls. While death-associated protein kinase () promoter methylation was not correlated with GC. Further analyses demonstrated that , and promoter methylation had a good diagnostic capacity in blood samples of GC versus non-tumor controls (: sensitivity = 63.2% and specificity = 97.5%, : sensitivity = 61.5% and specificity = 96.3%, : sensitivity = 82.0% and specificity = 89.0%). Our findings indicate that promoter methylation of the , and genes could be powerful and potential noninvasive biomarkers for the detection and diagnosis of GC in blood samples in clinical practices, especially gene. Further well-designed (multi-center) and prospective clinical studies with large populations are needed to confirm these findings in the future.
基因启动子甲基化已在胃癌(GC)中被报道。然而,基于血液的基因启动子甲基化作为GC检测的非侵入性生物标志物的潜在应用仍有待评估。因此,我们进行了这项分析,以确定11个肿瘤相关基因的启动子甲基化是否能成为GC血液样本中有前景的生物标志物。我们发现,与非肿瘤对照相比,细胞周期蛋白依赖性激酶抑制剂2A()、E-钙黏蛋白()、 runt相关转录因子3()、人MutL同源蛋白1()、RAS关联结构域家族蛋白1A()、细胞周期蛋白依赖性激酶抑制剂2B()、腺瘤性息肉病 coli()、谷胱甘肽S-转移酶P1()、TP53依赖性G2期阻滞介质候选物()和O6-甲基鸟嘌呤-DNA甲基转移酶()启动子甲基化在GC患者的血液样本中明显更高。而死亡相关蛋白激酶()启动子甲基化与GC无关。进一步分析表明,、和启动子甲基化在GC血液样本与非肿瘤对照中具有良好的诊断能力(:敏感性 = 63.2%,特异性 = 97.5%;:敏感性 = 61.5%,特异性 = 96.3%;:敏感性 = 82.0%,特异性 = 89.0%)。我们的研究结果表明,、和基因的启动子甲基化可能是临床实践中血液样本中检测和诊断GC的强大且潜在的非侵入性生物标志物,尤其是基因。未来需要进一步设计良好的(多中心)和前瞻性大样本临床研究来证实这些发现。