基于TCGA数据库分析胸苷酸合成酶基因在食管癌组织中的表达及临床意义  

Expression and clinical significance of thymidylate synthase gene in esophageal carcinoma based on TCGA database

作　　者：张文君 陈清江 张旭东[3] 唐灿伟 吴晓爽 李冲[1] 王妍杰 刘栋林 马珊珊[3] ZHANG Wenjun;CHEN Qingjiang;ZHANG Xudong;TANG Canwei;WU Xiaoshuang;LI Chong;WANG Yanjie;LIU Donglin;MA Shanshan(Department of Oncology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China)

机构地区：[1]新乡医学院第三附属医院肿瘤科,河南新乡453003 [2]新乡医学院,河南新乡453003 [3]郑州大学第一附属医院肿瘤科,河南郑州450052

出　　处：《新乡医学院学报》2023年第8期721-728,共8页Journal of Xinxiang Medical University

基　　金：国家自然科学基金面上项目(编号:82070210);河南省医学科技攻关重大项目(编号:SBGJ202001008)。

摘　　要：目的探讨胸苷酸合成酶(TYMS)基因在食管癌(ESCA)患者中的表达及其与临床特征和预后的关系。方法从癌症基因组图谱数据库下载ESCA患者的原始转录组测序数据、临床信息及临床病理学资料,应用t检验和χ^(2)检验评估TYMS基因在食管癌组织与正常组织间的表达差异,受试者操作特征(ROC)曲线评估TYMS基因对ESCA的诊断价值;Kaplan-Meier生存分析比较不同表达TYMS水平ESCA患者的无进展间隔(PFI)率、总生存(OS)率和疾病特异性生存(DSS)率;应用Cox回归分析和预后列线图确定TYMS基因对ESCA预后的评估价值;并使用单样本基因集合富集分析免疫浸润水平与TYMS基因表达的相关性。结果共获取173例样本的临床病理学资料,其中11例为正常样本,162例为ESCA样本。总样本中,ESCA组织中TYMS基因表达水平显著高于正常样本(t=6.344,P<0.001);在8例配对ESCA和邻近癌旁组织中,ESCA组织中TYMS基因表达水平显著高于邻近癌旁组织(t=6.866,P<0.001)。TYMS高表达组与TYMS低表达组患者的临床分期、病理分级、是否行放射治疗及是否为Barrett食管比较差异无统计学意义(P>0.05);2组患者的年龄、体质量及组织学分型比较差异有统计学意义(P<0.05)。ROC曲线显示,TYMS基因诊断ESCA的曲线下面积为0.949,95%置信区间为0.896~1.000,敏感度为0.909,特异度为0.791。TYMS基因高表达与TYMS基因低表达患者的OS率、DSS率和PFI率比较差异无统计学意义(HR=0.940、1.040、0.980,P>0.05)。在体质量>70 kg的ESCA患者中,TYMS基因高表达患者的OS率显著低于TYMS基因低表达患者(P<0.05);在非Barrett食管疾病的ESCA患者中,TYMS基因高表达患者的OS率显著低于TYMS基因低表达患者(P<0.05)。在不同T、N、M分期及病理分级、是否行放射治疗、不同年龄段、食管癌、Barrett食管疾病及体质量≤70 kg患者中,TYMS基因高表达与TYMS基因低表达患者的OS率比较差异无统计学意义(P>0.05)。从Objective To investigate the expression of thymidylate synthase(TYMS)gene in esophageal carcinoma(ESCA)and its relationship with clinical features and prognosis.Methods The original transcriptome sequencing data,clinical information and clinicopathological data of ESCA patients were downloaded from The Cancer Genome Atlas database,and the difference of the expression level of TYMS gene between esophageal cancer tissues and normal tissues was evaluated by t-test and Chi-square test.The diagnostic value of TYMS gene for ESCA was evaluated by receiver operating characteristic(ROC)curve.The progression-free interval(PFI)rate,overall survival(OS)rate and disease-specific survival(DSS)rate of ESCA with different TYMS expression levels were compared by Kaplan-Meier survival analysis.The prognostic value of TYMS gene for ESCA were determined by Cox regression analysis and prognosis nomogram.The correlation between immune infiltration level and TYMS gene expression level was analyzed by single sample gene collection enrichment analysis.Results Clinicopathological data of 173 samples were obtained,of which 11 were normal samples and 162 were ESCA samples.In total samples,the expression level of TYMS gene in ESCA tissues was significantly higher than that in normal samples(t=6.344,P<0.001).In 8 cases of paired ESCA and adjacent paracancer tissues,the expression level of TYMS gene in ESCA tissues was significantly higher than that in adjacent paracancer tissues(t=6.866,P<0.001).There was no significant difference in clinical stage,pathological grade,radiation therapy and Barrett esophagus between TYMS high expression group and TYMS low expression group(P>0.05).There were significant differences in age,body mass and tissue type between the two groups(P<0.05).ROC curve showed that the area under the curve of TYMS gene in the diagnosis of ESCA was 0.949,95%confidence interval was 0.896-1.000,the sensitivity was 0.909,and the specificity was 0.791.There was no significant difference in OS rate,DSS rate and PFI rate between the p

关 键 词：食管癌 胸苷酸合成酶 生物信息学 预后 免疫浸润 

分 类 号：R735.1[医药卫生—肿瘤]