TP53突变及其不同分型与晚期EGFR敏感突变肺腺癌一线EGFR-TKIs疗效的关联性分析  

Analysis on the correlation of TP53 mutations and their different variant forms with the efficacy of first-line treatment of EGFR-TKIs in patients with advanced EGFR-sensitive mutant lung adenocarcinoma

作　　者：李小芳[1] 隰成林 霍燃[1] 房国涛[1] 商琰红[1] LI Xiaofang;XI Chenglin;HUO Ran;FANG Guotao;SHANG Yanhong(Department of Medical Oncology,Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院肿瘤内科,保定071000

出　　处：《中国临床新医学》2024年第12期1339-1346,共8页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：河北大学附属医院青年科研基金项目(编号:2017Q005)。

摘　　要：目的探讨TP53突变及其不同分型与晚期表皮生长因子受体(EGFR)敏感突变肺腺癌患者一线使用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)疗效的关联性。方法收集TCGA数据库中的数据进行生物信息学分析。回顾性分析2017年12月至2022年12月河北大学附属医院肿瘤内科收治的152例晚期EGFR敏感突变(19 Del或21 L858R)肺腺癌患者的临床资料,均接受EGFR-TKIs治疗。分析TP53突变及其不同分型与EGFR-TKIs疗效的关联性。结果纳入分析的152例患者中存在EGFR-TP53共突变者105例。TP53突变型患者相较于野生型患者的无进展生存期(PFS)更短。错义突变、5~8外显子突变、破坏性突变、非破坏性突变患者相较于TP53野生型患者的PFS更短。在EGFR-TP53共突变患者中,TP53错义突变患者相较于非错义突变患者的PFS更短;TP53非破坏性突变患者相较于破坏性突变患者的PFS更短;5~8外显子突变患者相较于4/9/10外显子突变患者的PFS更短。结论相较于TP53野生型患者,TP53突变晚期EGFR敏感突变肺腺癌患者一线治疗的PFS更短,提示TP53突变是晚期EGFR敏感突变肺腺癌EGFR-TKIs疗效的负性预测因子。在EGFR-TP53共突变患者中,TP53错义突变、非破坏性突变、5~8外显子突变有更短的PFS。Objective To explore the correlation of TP53 mutations and their different variant forms with the efficacy of first-line treatment of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)in patients with advanced EGFR-sensitive mutant lung adenocarcinoma.Methods The data from The Cancer Genome Atlas(TCGA)database was collected for bioinformatics analysis.The clinical data of 152 patients with advanced EGFR-sensitive mutant(19 Del or 21 L858R)lung adenocarcinoma who were admitted to Department of Medical Oncology,Affiliated Hospital of Hebei University from December 2017 to December 2022 were retrospectively analyzed.All the patients were treated with EGFR-TKIs.The correlation of TP53 mutations and their different variant forms with the efficacy of EGFR-TKIs was analyzed.Results Of the 152 patients included in the analysis,105 patients had EGFR-TP53 co-mutations.The patients with TP53 mutations had shorter progression-free survival(PFS)than those with TP53 wild-type.The patients with missense mutations,mutations in exons 5-8,disruptive mutations,and non-disruptive mutations had shorter PFS than those with TP53 wild-type.In the patients with EGFR-TP53 co-mutations,the patients with TP53 missense mutations had shorter PFS than those with non-missense mutations,and the patients with non-disruptive TP53 mutations had shorter PFS than those with disruptive TP53 mutations,and the patients with mutations in exons 5-8 had shorter PFS than those with mutations in exon 4/9/10.Conclusion The advanced EGFR-sensitive mutant lung adenocarcinoma patients with TP53 mutations who receive first-line treatment have shorter PFS than those with TP53 wild-type,suggesting that TP53 mutations are negative predictor of efficacy of EGFR-TKIs in the advanced EGFR-sensitive mutant lung adenocarcinoma patients.In the patients with EGFR-TP53 co-mutations,the patients with TP53 missense mutations,non-disruptive mutations,and mutations in exons 5-8 have shorter PFS.

关 键 词：表皮生长因子受体 TP53突变 共突变 肺腺癌 预后 

分 类 号：R734.2[医药卫生—肿瘤]