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基于时钟基因启动子区甲基化的胃癌患者预后预测模型的建立与验证
引用本文:黄一波,牛英群,黄国强,胡如英.基于时钟基因启动子区甲基化的胃癌患者预后预测模型的建立与验证[J].中华全科医学,2022,20(1):43-46.
作者姓名:黄一波  牛英群  黄国强  胡如英
作者单位:1.浙江中医药大学附属二院普外科,浙江 杭州 310005
基金项目:浙江省医药卫生科技计划项目(2017KY517,2014KYB180)。
摘    要:  目的  建立基于时钟基因启动子区甲基化的胃癌患者预后的预测模型并验证其效能。  方法  选取2015年1月—2018年1月浙江中医药大学附属二院收治的胃癌患者459例,术后随访2年,根据复发情况分为复发组和未复发组。对比2组患者一般资料、手术相关资料、时钟基因启动子区甲基化情况,行多因素logistic回归分析研究复发的独立影响因素,使用R软件建立复发的预测模型,并验证其效能。  结果  随访过程中5例患者失访,剩余454例患者中,217例肿瘤复发列为复发组,其余237例未复发列为非复发组,胃癌复发率为47.80%(217/454)。2组分化程度、淋巴结转移、肿瘤生长方式以及per1、per2、cry1、clock时钟基因启动子区甲基化差异有统计学意义(均P < 0.05)。多因素logistic回归分析结果显示,分化程度(OR=0.519,P=0.006)、淋巴结转移(OR=2.365,P<0.001)、肿瘤生长方式(OR=0.616,P=0.036)、per1(OR=24.108,P<0.001)、per2(OR=2.152,P=0.008)、cry1(OR=3.131,P<0.001)、clock(OR=1.676,P=0.024)是胃癌复发的独立影响因素。预测模型预测复发发生的一致性指数为0.906(95% CI:0.879~0.938)。  结论  分化程度、淋巴结转移、肿瘤生长方式及per1、per2、cry1、clock时钟基因启动子区甲基化作为影响因素建立的预测模型可有效预测胃癌的复发,并具有较好的应用价值。 

关 键 词:胃癌    时钟基因    启动子区    甲基化    预测模型
收稿时间:2020-07-09

Establishment and verification of a prognostic model for patients with gastric cancer based on clock gene promoter methylation
Authors:HUANG Yi-bo  NIU Ying-qun  HUANG Guo-qiang  HU Ru-ying
Affiliation:Department of General Surgery, the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310005, China
Abstract:Objective To establish and certificate a prognostic model for gastric cancer patients based on methylation of the promoter region of the clock gene.Methods A total of 459 patients with gastric cancer admitted to the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2015 to January 2018 were selected.They were followed up for 2 years after operation and were divided into the recurrence group and non-recurrence group according to the recurrence.The differences in the general data,surgery-related data and methylation frequency of the clock gene promoter region between the two groups were compared.Multivariate logistic regression analysis was performed to determine the independent influencing factors of recurrence,and R software was used to establish a predictive model of recurrence and verify its efficacy.Results During follow-up,5 cases were lost to follow-up.Among the remaining 454 patients,217 had recurrence and were classified as the recurrence group,and the remaining 237 cases without recurrence were classified as the non-recurrence group.The recurrence rate of gastric cancer was 47.80%(217/454).There were statistically significant differences in the degree of differentiation,lymph node metastasis,tumour growth pattern and methylation frequency of the per1,per2,cry1 and clock gene promoter regions between the two groups(P<0.05).Multivariate logistic regression analysis showed that the degree of differentiation(OR=0.519,P<0.05),lymph node metastasis(OR=2.365,P<0.05),tumour growth pattern(OR=0.616,P<0.05),per1(OR=24.108,P<0.05),per2(OR=2.152,P<0.05),cry1(OR=3.131,P<0.05)and clock(OR=1.676,P<0.05)were independent factors affecting gastric cancer recurrence.The prediction model showed that the consistency index of recurrence was 0.906(95%CI:0.879-0.938).Conclusion The degree of differentiation,lymph node metastasis,tumour growth pattern and methylation of the per1,per2,cry1 and clock gene promoter regions as influencing factors can effectively predict the recurrence of gastric cancer,and have good application value.
Keywords:Gastric cancer  Clock gene  Promoter  Methylation  Prediction model
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