TP53和RB1基因突变状态对广泛期小细胞肺癌患者免疫治疗疗效的预测价值:一项临床回顾性分析  

Prognostic value of TP53 and RB1 gene mutation status on the efficacy of immunotherapy in patients with extensive-stage small cell lung cancer:a retrospective cohort study

作　　者：全溪铷 陆舜[1] QUAN Xiru;LU Shun(Department of Oncology,Shanghai Chest Hospital/Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China)

机构地区：[1]上海市胸科医院,上海交通大学医学院附属胸科医院肿瘤内科,上海200030

出　　处：《肿瘤》2024年第6期683-692,共10页Tumor

基　　金：国家自然科学基金(82030045)

摘　　要：目的:探究TP53、RB1基因突变状态对广泛期小细胞肺癌(small-cell lung cancer,SCLC)患者免疫治疗疗效的影响。方法:本研究回顾性分析了从2019年8月—2022年11月在上海市胸科医院肿瘤内科接受免疫治疗的广泛期SCLC患者的临床病理资料,并对其中具有下一代测序(next generationsequencing,NGS)数据的患者进行了深入探讨。通过应用Kaplan-Meier生存分析法和COX比例风险模型,本研究评估了TP53和RB1基因突变状态对广泛期SCLC患者预后的影响和及其临床意义。结果:本研究初始共纳入了110例接受免疫治疗并具有NGS数据的广泛期SCLC患者。根据TP53、RB1基因的突变状态,将纳入患者分为3组:TP53/RB1共突变(TP53mut/RB1mut)组(87例,79.1%),TP53突变/RB1野生型(TP53mut/RB1wt)组(20例,18.2%),TP53/RB1均野生型(TP53wt/RB1wt)组(3例,2.7%)。为避免组内人数太少对结果造成影响,最终排除了TP53/RB1均野生型组的3例患者,将剩余107例患者分为TP53/RB1共突变组和TP53突变/RB1野生型组,以进行后续分析。研究结果发现,与TP53/RB1共突变相比,TP53突变/RB1野生型能够明显缩短广泛期SCLC患者接受免疫治疗后的无进展生存期(progression-free survival,PFS)(P=0.048)和总生存期(overall survival,OS)(P=0.027);单因素COX比例风险模型分析结果表明TP53突变/RB1野生型是广泛期SCLC患者免疫治疗OS的影响因素[HR=1.827(95%CI:1.061~3.149),P=0.030];多因素COX比例风险模型分析结果表明TP53突变/RB1野生型是影响广泛期SCLC患者免疫治疗PFS的独立危险因素[HR=1.812(95%CI:1.033~3.177),P=0.038],而ECOGPS评分≥1是影响广泛期SCLC患者免疫治疗OS的独立危险因素[HR=2.579(95%CI:1.073~6.196),P=0.034]。结论:在接受免疫治疗的广泛期SCLC患者中,相较于TP53/RB1共突变患者,TP53突变/RB1野生型患者的免疫治疗效果和预后情况更差,且TP53突变/RB1野生型是影响广泛期SCLC患者免疫治疗PFS的独立危险因素。Objective:To explore the impact of TP53 and RB1 gene mutation status on the efficacy of immunotherapy in patients with extensive-stage small cell lung cancer(SCLC).Methods:This study retrospectively analyzed the clinical and pathological data of patients with extensive-stage SCLC who received immunotherapy at the department of oncology of Shanghai Chest Hospital from August 2019 to November 2022.A detailed investigation was conducted on patients with next-generation sequencing(NGS)data.By applying Kaplan-Meier survival analysis and COX proportional hazards model,the study evaluated the impact of TP53 and RB1 gene mutation status on the prognosis and clinical significance of patients with extensive-stage SCLC.Results:A total of 110 patients with extensive-stage SCLC who received immunotherapy and had NGS data were enrolled initially.Based on the TP53 and RB1 gene mutation status,the patients were divided into three groups:TP53/RB1 co-mutation(TP53mut/RB1mut)in 87 cases(79.1%),TP53 mutation/RB1 wild-type(TP53mut/RB1wt)in 20 cases(18.2%),and TP53/RB1 both wild-type(TP53wt/RB1wt)in 3 cases(2.7%).To avoid the influence of a small sample size,the final analysis excluded the 3 patients with TP53/RB1 both wild-type group,and the remaining 107 patients were divided into two groups for further analysis:TP53/RB1 co-mutation group and TP53 mutation/RB1 wild-type group.The study found that compared to TP53/RB1 co-mutation,TP53 mutation/RB1 wild-type significantly shortened the progression-free survival(PFS)(P=0.048)and overall survival(OS)(P=0.027)of patients with extensive-stage SCLC receiving immunotherapy;the results of univariate COX proportional hazards model analysis indicated that TP53 mutation/RB1 wild-type was a prognostic factor for OS in patients with extensive-stage SCLC receiving immunotherapy[HR=1.827(95%CI:1.061-3.149),P=0.030];the results of multivariate COX proportional hazards model analysis showed that TP53 mutation/RB1 wild-type was an independent risk factor for PFS[HR=1.812(95%CI:1.033-3.177),P=0.038],an

关 键 词：广泛期小细胞肺癌 免疫治疗 TP53 RB1 基因突变 

分 类 号：R734.2[医药卫生—肿瘤]