采用cBiPortal数据库分析消化系统易突变基因变异在食管癌胃癌中的临床意义

Clinical significance of igestive system mutation-prone gene variants in esophagus and gastric cancer by cBioPortal database

目的研究人类消化系统易突变基因〔包括TP53、ERBB2、PIK3CA、KRAS、EGFR、VEGFA、PTEN、MTOR、MET、KDR、AKT1基因〕突变在食管癌胃癌中的临床意义。方法从cBiPortal网站公开资料中下载美国癌症基因图谱(TCGA)数据库提供的2803例食管癌胃癌患者的2870份样本的基因表达谱和临床资料,并对相关信息进行分析,采用cBiPortal工具进行基因突变和患者生存分析。结果①TP53基因的突变率最高,其次是ERBB2、PIK3CA和KRAS基因,其余基因的突变率均低于10%。②按病理分类分组,分析基因的改变频率均为40.00%~95.05%,在基因改变方式中以基因突变的发生率最高,其次是多重改变,扩增和深度删除的改变方式较少发生,发生率均低于10%。③TP53和PTEN基因在食管癌胃癌中互斥趋势较显著(P<0.001,q<0.001)。④确诊基因变异的患者数是未变异患者数的约4.7倍。⑤食管鳞状细胞癌基因变异患者的中位生存时间最长(39.9个月),食管腺癌基因变异患者的中位生存时间最短(25.8个月)。⑥与本研究关联的其他高频突变基因中,以胃腺癌的基因频率改变最显著,且这些基因的改变频率具有高度一致性。结论食管癌胃癌患者确诊病例的基因改变具有普遍性,其中TP53基因突变率最高,TP53与PTEN基因有互斥趋势,食管鳞状细胞癌基因变异患者较食管腺癌基因变异患者的生存率高,通过cBiPortal工具分析可挖掘数据库中未知的潜在规律,为肿瘤的诊断治疗提供更可靠依据。

Objective To study the clinical significance of igestive system mutation-prone genes[TP53,V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2(ERBB2),PIK3CA,Kirsten ratsarcoma viral oncogene homolog(KRAS),epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),phosphatase and tensin homolog(PTEN),mammalian target of rapamycin(MTOR),mesenchymal-epithelial transition factor(MET),kinase insert domain receptor(KDR)and AKT1 genes]mutations in esophagealand gastric cancer.Methods The gene expression profile and clinical data information of 2870 samples from 2803 patients with esophagus and gastric cancer provided in The Cancer Gene Atlas(TCGA)database were downloaded from the cBiPortal website,and the cBiPortal tools were useed to analysze the gene mutation and survival situation of patients.Results①The mutation rate of TP53 gene was the highest,followed by ERBB2,PIK3CA and KRAS genes.The mutation rates of other genes were all lower than 10%.②According to pathological classification,the frequency of gene changes was between 40.00%to 95.05%.Among gene multiple changes,the rate of gene mutation was the highest,followed by multiple alterations,amplification and deep deletion changes occurring rarely,which were all less than 10%.③TP53 and PTEN genes had significant tendencies to mutually exclusive in esophageal and gastric cancer(P<0.001,q<0.001).④The number of patients with confirmed cancer mutation was about 4.7 times of those in without mutation.⑤The patients with esophageal squamous cell carcinoma gene variant had the longest median survival time(39.92 months),and the patients with esophageal adenocarcinoma gene variant had the shortest median survival time(25.78 months).⑥In other high-frequency mutation genes associated with this study,the frequency of gene changes in stomach adenocarcinoma was the most significant,and the frequency of gene changes in these genes was highly consistent.Conclusions The genetic changes in the confirmed cases of esophageal and gastric cancer are universal.The mutation rate of TP53 is the highest,TP53 and PTEN genes have a tendency of mutual exclusivity.The patinets with esophageal squamous cell carcinoma gene variant have higher survival rates than those with esophageal adenocarcinoma gene variant.The unknown underlying laws in the database provide a more reliable basis for the diagnosis and treatment of tumors,which can be discovered by cBiPortal analysis tools.