基于生物钟基因的胃癌预后风险评估模型的建立  

Establishment of prognostic risk evaluation model for gastric cancer based on clock genes

作　　者：金悦 卢文卿 包博文 郑雪莹 佟笛 车晓芳[1,2,3] JIN Yue;LU Wenqing;BAO Bowen;ZHENG Xueying;TONG Di;CHE Xiaofang(The First Hospital of China Medical University,Shenyang 110001,China;不详)

机构地区：[1]中国医科大学附属第一医院,沈阳110001 [2]辽宁省肿瘤药物与生物治疗重点实验室 [3]辽宁省恶性肿瘤临床医学研究中心

出　　处：《山东医药》2021年第8期6-10,共5页Shandong Medical Journal

基　　金：国家自然科学基金面上项目(81972751);辽宁省重点研发指导计划资源平台建设项目(2018225060);沈阳市重大科技创新研发计划项目(19-112-4-099)。

摘　　要：目的分析影响胃癌患者预后的生物钟基因,建立基于生物钟基因的胃癌预后风险评估模型。方法下载NCBI中GSE62254数据集,筛选出298例胃癌患者样本。分析不同生物钟基因表达水平的胃癌患者总生存期(OS)的差异,筛选影响胃癌患者OS的关键生物钟基因,分析关键生物钟基因表达水平与胃癌临床病理参数的关系。在关键生物钟基因及性别、年龄、浸润深度、淋巴结转移、远处转移、腹膜转移等临床病理参数中筛选胃癌预后的独立影响因素,在此基础上构建胃癌预后风险(RS)评估模型,绘制RS评分预测胃癌预后的ROC曲线,计算曲线下面积和约登指数最大时的敏感度和特异度。结果生物种基因CLOCK、PER1、PER3、CRY2、NPAS2、RORA高表达的胃癌患者较低表达者OS更短,TIMELESS高表达的胃癌患者较低表达者OS更长(P均<0.05)。在生物钟基因中,PER1、CRY2和RORA是胃癌患者OS的独立危险因素;PER1高表达与低龄、浸润深度较深、TNM分期较晚、腹膜转移有关,CRY2高表达与浸润深度较深、TNM分期较晚、淋巴结转移、腹膜转移有关,RORA高表达与低龄、浸润深度较深、TNM分期较晚、淋巴结转移、远处转移、腹膜转移有关(P均<0.05)。多因素分析结果显示,淋巴结转移、远处转移、腹膜转移和PER1高表达是影响胃癌预后的独立危险因素(P均<0.05)。根据公式RS=0.692×淋巴结转移+0.747×远端转移+1.013×腹膜转移+0.638×PER1表达建立胃癌预后风险评估模型。RS评分预测胃癌预后的ROC曲线下面积为0.817,敏感度为0.642、特异度为0.899。结论生物钟基因PER1、CRY2、RORA与胃癌预后密切相关,基于PER1联合淋巴结转移、远端转移、腹膜转移等临床病理参数建立的胃癌预后风险评估模型具有较好的应用效能。Objective To analyze the circadian clock genes which influences the prognosis of gastric cancer(GC)patients and to construct the prognostic risk evaluation model for gastric cancer based on clock genes.Methods GSE62254 dataset from NCBI was downloaded to screen out 298 samples of GC patients.The difference in overall survival(OS)of GC patients with different expression levels of circadian clock genes was analyzed to screen out key circadian clock genes of GC,and then the relationship between the expression levels of key circadian clock genes and the clinicopathological parameters of GC was analyzed.The independent prognostic factors screened out from the clinicopathological parameters,such as key circadian clock genes,gender,age,tumor invasion,lymph node metastasis,distant metastasis and peritoneal metastasis,were analyzed,and the prognostic risk(RS)evaluation model of GC was constructed based on them.The ROC curve of RS score in predicting GC prognosis was drawn,and the area under the curve and the sensitivity and specificity at the maximum of Youden index were calculated.Results The OS of GC patients with the high expression of CLOCK,PER1,PER3,CRY2,NPAS2 and RORA was shorter than that of patients with the low expression;the OS of GC patients with the high expression of TIMELESS was longer than that of patients with the low expression(all P<0.05).Among the clock genes,PER1,CRY2,and RORA were independent risk factors for GC.PER1 high expression was related to low age,deeper tumor invasion,later TNM stage and peritoneal metastasis;CRY2 high expression was related to deeper tumor invasion,later TNM stage,lymph node metastasis,and peritoneal metastasis;RORA high expression was related to low age,deeper tumor invasion,later TNM stage,lymph node metastasis,distant metastasis,and peritoneal metastasis(all P<0.05).Multivariate analysis showed that lymph node metastasis,distant metastasis,peritoneal metastasis and high expression of PER1 were independent risk factors affecting the prognosis of GC(all P<0.05).According to

关 键 词：胃癌 生物钟基因 PER1基因 预后评估 

分 类 号：R735.2[医药卫生—肿瘤]