基于癌症基因组图谱的预测非小细胞肺癌预后相关突变基因的挖掘与分析

Mining and analysis of prognosis-related mutant gene groups in non-small cell lung cancer based on the Cancer Genome Atlas

目的基于癌症基因组图谱(TCGA)挖掘和探讨突变基因与非小细胞肺癌(NSCLC)临床预后的相关性,以期为NSCLC预后提供敏感有效的生物标志物。方法2021年5月25日,从TCGA(https://portal.gdc.cancer.gov/)中下载确诊为NSCLC的患者资料,其中包括924例肺腺癌(LUAD)患者[433例有单核苷酸变异(SNV)数据,535例癌组织和59例正常组织有信使核糖核酸(mRNA)表达信息]和994例肺鳞癌(LUSC)患者(475例有SNV数据,502例癌组织和49例正常组织有mRNA表达信息)。采用瀑布图和Wilcoxon秩和检验挖掘分析在NSCLC患者中突变频率较高,且能够显著影响其表达的基因,最后通过Kaplan-Meier法进行生存分析,寻找能够作为NSCLC预后标志物的基因。结果在LUAD中,肿瘤蛋白P53(TP53)、心肌型兰尼定受体2(RYR2)和低密度脂蛋白受体相关蛋白1B(LRPIB)基因突变频率高,且突变后mRNA表达低于野生型患者,差异有统计学意义(P<0.05)。在LUSC中,LRP1B和含Xin肌动蛋白结合重复序列的蛋白2(XIRP2)基因突变频率高,且突变后mRNA表达低于野生型患者,差异有统计学意义(P<0.05)。最后通过Kaplan-Meier生存分析后,只有TP53突变可以作为肺腺癌的临床预后不良的标志物,LRP1B突变可以作为肺鳞癌的临床预后不良的标志物。结论TP53和LRP1B突变有可能作为LUAD和LUSC的预后标志物。

Objective Based on the Cancer Genome Atlas(TCGA),the correlation between mutated genes and the clinical prognosis of non-small cell lung cancer(NSCLC)was explored,in order to provide sensitive and effective biomarkers for the prognosis of NSCLC.Methods On May 25,2021,the data of patients diagnosed with NSCLC was downloaded from TCGA(https://portal.gdc.cancer.gov/),including 924 patients with lung adenocarcinoma(LUAD)(433 patients with single nucleotide variant[SNV]data,535 cancer tissues and 59 normal tissues with mRNA expression information)and 994 lung squamous cell carcinoma(LUSC)patients(475 SNV data,502 cancer tissues and 49 normal tissues with mRNA expression information).The waterfall map and Wilcoxon test method were used to mine and analyze the genes with high mutation frequency in NSCLC patients and which could significantly affect their expression.Finally,Kaplan-Meier survival analysis was performed to find genes that could serve as prognostic markers for NSCLC.Results In LUAD,the mutation frequency of tumor protein P53(TP53),myocardial Ranidine receptor 2(RYR2)and low density lipoprotein receptor-associated protein 1B(LRPIB)genes were high,and the mRNA expression after mutation was lower than that of wild-type patients,with statistical significance(P<0.05).In LUSC,the mutation frequency of LRP1B and Xin-containing actin binding repeat protein 2(XIRP2)gene was high,and mRNA expression after mutation was lower than that of wild-type patients,with statistical significance(P<0.05).However,only TP53 mutation could be used as clinical prognostic marker for lung adenocarcinoma,and LRP1B mutation could be used as clinical prognostic marker for lung squamous cell carcinoma by Kaplan-Meier survival analysis.Conclusion TP53 and LRP1B mutations can be used as prognostic markers for LUAD and LUSC,respectively.