非小细胞肺癌组织的KIF11水平及临床意义

Level and clinical significance of KIF11 in non-small cell lung cancer tissues

目的探讨非小细胞肺癌(NSCLC)组织中驱动蛋白家族成员11(KIF11)的水平及临床意义。方法利用GEPIA分析癌症基因组图谱(TCGA)数据库中NSCLC(483例腺癌和486例鳞癌)组织的KIF11水平,从人类肿瘤相关基因表达汇编(GEO)数据库下载肺癌样本数据集GSE31210、GSE30219和GSE31908的KIF11表达谱数据;采用实时定量PCR检测本院2016年3月至2018年12月手术切除的NSCLC患者癌组织及配对癌旁组织共86对,分析KIF11水平与NSCLC临床病理特征的关系并采用受试者工作特征(ROC)曲线评价KIF11对NSCLC的诊断效能;采用GEPIA和Kaplan-Meier Plotter在线分析KIF11水平与NSCLC预后的关系。结果TCGA数据库中483例腺癌和486例鳞癌组织的KIF11水平均高于正常组织(P<0.05);GSE31210、GSE30219和GSE31908数据集中癌组织的KIF11水平分别为553.437±32.961、6.760±1.351和4.824±0.109,均高于对应正常组织(P<0.05)。86例NSCLC组织的KIF11水平为3.405±0.172,高于癌旁组织的1.038±0.074(P=0.001);ROC曲线分析显示组织KIF11水平诊断NSCLC的曲线下面积为0.906(95%CI:0.861~0.950,P<0.001);KIF11水平与NSCLC的性别、年龄、吸烟史和病理类型均无关(P>0.05),而与肿瘤直径、淋巴结转移、分化程度和TNM分期有关(P<0.05)。GEPIA在线分析显示,KIF11水平与NSCLC总体及不同病理类型的无病生存期无关(P>0.05),但与NSCLC总体及肺腺癌的总生存期(OS)有关,其中KIF11高水平者的OS较差(HR=1.2,P=0.035;HR=1.7,P<0.001)。Kaplan-Meier Plotter在线分析显示,KIF11高水平者的中位OS为47.9个月,低于低水平的87.7个月(HR=1.52,95%CI:1.4~1.73,P<0.001),进一步分析显示GSE31210、GSE30219数据集中高水平者的中位OS均低于低水平者(P<0.05)。结论NSCLC组织中KIF11高表达,对肿瘤大小、淋巴结转移、分化程度和TNM分期有一定预测价值,高水平者的预后较差,在NSCLC诊治和预后预测上有一定前景。

Objective To investigate the level and clinical significance of kinesin family member 11(KIF11)in non-small cell lung cancer(NSCLC)tissues.Methods The KIF11 level of NSCLC tissues(483 cases of adenocarcinoma and 486 cases of squamous cell carcinoma)in The Cancer Genome Atlas(TCGA)project was analyzed by GEPIA.The KIF11 expression profile data of GSE31210,GSE30219 and GSE31908 were downloaded from the human tumor related Gene Expression Omnibus(GEO)database.Using real-time quantitative PCR,86 pairs of cancer tissues and matched paracancerous tissues from NSCLC patients in our hospital between March 2016 and December 2018 were analyze.The relationship between KIF11 level and clinicopathological characteristics of NSCLC was further investigated,and the receiver operating characteristic(ROC)curve was applied to assess the diagnostic efficacy of KIF11 on NSCLC.GEPIA and Kaplan-Meier Plotter were used to analyze the relationship between KIF11 level and the prognosis of NSCLC.Results The KIF11 levels in 483 cases of lung adenocarcinoma and 486 cases of lung squamous cell carcinoma tissues in TCGA database were higher than those in normal tissues(P<0.05).KIF11 levels in GSE31210,GSE30219 and GSE31908 data sets were 553.437±32.961,6.760±1.351 and 4.824±0.109,higher than those in corresponding normal tissues(P<0.05).The KIF11 level in 86 NSCLC tissues was 3.405±0.172,higher than 1.038±0.074 in paracancerous tissues(P=0.001).ROC curve analysis showed that the area under curve of tissue KIF11 in diagnosing NSCLC was 0.906(95%CI:0.861-0.950,P<0.001).KIF11 level was independent of sex,age,smoking history and pathological type of NSCLC(P>0.05),but related to tumor diameter,lymph node metastasis,differentiation and TNM stage(P<0.05).GEPIA online analysis showed that KIF11 level was not related to disease-free survival in total NSCLC and different pathological types(P>0.05),but related to overall survival(OS)of total NSCLC and lung adenocarcinoma,among which higher level of KIF11 was worse(HR=1.2,P=0.035;HR=1.7,P<0.001).Kaplan-Meier Plotter online analysis showed that the median OS of patients with high-level KIF11 was 47.9 months,lower than 87.7 months of patients with low-level(HR=1.52,95%CI:1.40-1.73,P<0.001).Further analysis showed that the median OS of patients with high-level KIF11 in GSE31210 and GSE30219 data sets was lower than that of patients with low-level(P<0.05).Conclusion KIF11 is highly expressed in NSCLC tissues,which has a certain predictive value for tumor size,lymph node metastasis,differentiation and TNM stage.The prognosis of patients with high-level KIF11 is poor,indicating a certain prospect in the diagnosis and treatment of NSCLC.