Li Zhi, Guo Zhiqiang
Physical examination center, Gansu Gem Flower Hospital, Lanzhou petrochemical general hospital, Lanzhou, 730060, Gansu, China.
Medical section, Gansu Gem Flower Hospital, Lanzhou petrochemical general hospital, Lanzhou, 730060, Gansu, China.
Pathol Oncol Res. 2020 Apr;26(2):1057-1062. doi: 10.1007/s12253-019-00658-5. Epub 2019 Apr 15.
Hypermethylation is epigenetic alteration, well known for gene silencing. CHD1 gene is known as invasion and tumor suppressor gene, decreased expression due to hypermethylation could promote tumor cell invasion and metastasis. Present study designed to investigate the CDH1 gene promoter hypermethylation status by methylation specific polymerase chain reaction in 100 newly diagnosed gastric cancer patients. 53% of hypermethylation was observed in DNA extracted from blood in Gastric cancer patients while 66% was observed in serum based DNA. Significant differences in CDH1gene promoter hypermethylation was observed in serum based DNA extracted from Gastric cancer patients. Patients in early stage (I & II) vs advanced stage (III & IV), distant organ metastases vs no metastases had 60% vs 7% and 42% 24% of CDH1 promoter hypermethylation in serum DNA (p = 0.006, 0.001) respectively. Patients who were with lymph node invasion, loss of appetite, loss of weight had 55%, 47%, 61% CDH1 gene promoter hypermethylation compare to who were not with lymph node invasion, loss of appetite, loss of weight had 11%, 19%, 5% of hypermethylation and these differences was found to be significant. Strong association was observed with overall median survival of patients (p < 0.0001). Patients who had CDH1 gene promoter hypermethylation in serum based DNA showed poor overall median survival (14.3 months) and unmethylated patients had better overall median survival (33.2 months). CDH1 hypermethylation status was found to be associated with advancement of disease, distant organ metastases and lymph node invasion in Gastric cancer patients.
高甲基化是一种表观遗传改变，以基因沉默而闻名。CHD1基因是一种侵袭和肿瘤抑制基因，由于高甲基化导致的表达降低可促进肿瘤细胞的侵袭和转移。本研究旨在通过甲基化特异性聚合酶链反应调查100例新诊断胃癌患者中CDH1基因启动子的高甲基化状态。在胃癌患者血液中提取的DNA中观察到53%的高甲基化，而在基于血清的DNA中观察到66%的高甲基化。在从胃癌患者中提取的基于血清的DNA中观察到CDH1基因启动子高甲基化存在显著差异。早期（I和II期）与晚期（III和IV期）患者、远处器官转移与无转移患者的血清DNA中CDH1启动子高甲基化分别为60%和7%、42%和24%（p = 0.006，0.001）。有淋巴结侵犯、食欲不振、体重减轻的患者CDH1基因启动子高甲基化分别为55%、47%、61%，而无淋巴结侵犯、食欲不振、体重减轻的患者高甲基化分别为11%、19%、5%，这些差异具有显著性。观察到与患者的总中位生存期有很强的相关性（p < 0.0001）。基于血清DNA中CDH1基因启动子高甲基化的患者总中位生存期较差（14.3个月），未甲基化的患者总中位生存期较好（33.2个月）。发现CDH1高甲基化状态与胃癌患者的疾病进展、远处器官转移和淋巴结侵犯有关。
