晚期胃癌患者血浆RUNX3和p16基因甲基化与化疗疗效的相关性  

Methylation of plasma RUNX3 and p16 genes in patients with gastric cancer and its correlation with chemotherapy efficacy

作　　者：孙成晖 曾奇[2] 孙钦文 Sun Chenghui;Zeng Qi;Sun Qinwen(Department of Oncology,Yangchun People's Hospital,Yangchun 529600,China;Cancer Center,The Fifth Affiliated Hospital of Sun Yat Sen University,Guangzhou 519000,China)

机构地区：[1]阳春市人民医院肿瘤科,广东阳春529600 [2]中山大学附属第五医院肿瘤中心,广东广州519000

出　　处：《实用肿瘤杂志》2020年第2期145-150,共6页Journal of Practical Oncology

基　　金：阳江市卫计局科技计划项目(2015040)。

摘　　要：目的探讨晚期胃癌患者血浆RUNT相关转录因子3(human RUNT-related transcription factor 3,RUNX3)和p16基因甲基化与临床病理特征和氟尿嘧啶化疗敏感性的关系。方法收集行一线氟尿嘧啶联合化疗的晚期胃癌患者67例和体检健康42例。应用甲基化特异性PCR法检测血浆中RUNX3和p16基因甲基化,分析基因甲基化和临床病理特征、化疗疗效的关系。结果化疗前胃癌患者p16和RUNX3的甲基化频率均高于对照组[61.2%(41/67)vs 0.0%(0/42),70.1%(47/67)vs 11.9%(5/42);均P<0.01]。化疗后胃癌患者p16和RUNX3的甲基化频率分别降低至47.8%(32/67;χ^2=5.05,P=0.025)和47.8%(38/67;χ^2=2.61,P=0.106)。以胃为主要肿瘤部位的患者血浆标本中p16和RUNX3的甲基化频率均高于以胃食管交界处为主要肿瘤部位的患者(均P<0.05)。p16和RUNX3甲基化阳性患者对氟尿嘧啶化疗的应答率均低于甲基化阴性患者(17.1%vs 42.3%,P=0.023;19.1%vs45.0%,P=0.029)。结论p16和RUNX3的甲基化在胃癌患者血浆中较为常见且特异性强,二者与患者对氟尿嘧啶化疗的反应密切相关。Objective To investigate the correlation of plasma RUNT-related transcription factor 3(RUNX3)and p16 gene methylation to chemosensitivity in patients with gastric cancer.Methods Sixty-seven patients with gastric cancer treated with first-line fluorouracil-based combinative chemotherapy and 42 healthy controls were selected.The methylation of RUNX3 and p16 genes in patients’plasma was detected by methylation-specific PCR.Results The methylation frequency of p16 and RUNX3 in patients with gastric cancer before chemotherapy was higher than that in the control group[61.2%(41/67)vs 0.0%(0/42),70.1%(47/67)vs 11.9%(5/42);both P<0.01].After chemotherapy,the methylation frequency of p16 and RUNX3 in patients with gastric cancer decreased significantly to 47.8%(32/67;χ^2=5.05,P=0.025)and 47.8%(38/67;χ^2=2.61,P=0.106).Patients with stomach as the main tumor site had higher plasma methylation frequency of p16 and RUNX3 than those with gastroesophageal junction as the main tumor site(both P<0.05).The response rates of p16 and RUNX3 methylationpositive patients to fluorouracil chemotherapy were significantly lower than those of methylation-negative patients(17.1%vs 42.3%,P=0.023;19.1%vs 45.0%,P=0.029).Conclusions Methylation of p16 and RUNX3 in plasma is more common and highly specific in patients with gastric cancer and can affect patients’response to chemotherapy.

关 键 词：胃肿瘤/病理学 胃肿瘤/血液 胃肿瘤/药物疗法 基因 p16 基因表达 甲基化 转录因子 氟尿嘧啶/治疗应用 药物疗法 联合 治疗结果 

分 类 号：R735.2[医药卫生—肿瘤] R730.23[医药卫生—临床医学]