上皮细胞增殖通路基因对老年非小细胞肺癌患者免疫治疗预后的预测作用  

The predictive value of the epithelial cell proliferation pathway genes for the prognosis of elderly non-small cell lung cancer patients receiving immunotherapy

作　　者：杨帆 张萍[2] 高佳仪 袁月 王雪 何柳儿 李琳 Yang Fan;Zhang Ping;Gao Jiayi;Yuan Yue;Wang Xue;He Liuer;Li Lin(Peking University Fifth School of Clinical Medicine,Beijing 100730,China;Department of Medical Oncology,Beijing Hospital,National Center of Gerontology Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]北京大学第五临床医学院,北京100730 [2]北京医院肿瘤内科国家老年医学中心中国医学科学院老年医学研究院,北京100730

出　　处：《中华老年医学杂志》2023年第4期430-434,共5页Chinese Journal of Geriatrics

基　　金：中国医学科学院医学与健康科技创新工程项目"肺癌的精准治疗研究"(2021-I2M-1-012)。

摘　　要：目的探讨上皮细胞增殖(ECP)通路相关基因对老年非小细胞肺癌患者免疫治疗预后及疗效的提示作用。方法2022年10月回顾性分析POPLAR及OAK临床研究中年龄≥70岁、接受免疫治疗的老年患者106例,依据突变基因情况将患者分为ECP通路相关基因突变(ECP突变组)25例和相关基因未突变(ECP未突变组)81例。主要研究终点为患者总生存时间(OS)和无进展生存时间(PFS)。分别比较两组患者生存和疗效差异,并对各临床因素和通路涉及基因进行亚组分析。经Pyclone算法推算各患者主克隆及亚克隆分布并比较生存差异。结果ECP突变组与ECP未突变组患者比较,mOS缩短(10.9个月比17.1个月,HR=1.84,95%CI:1.09~3.08,P<0.05),mPFS亦缩短(2.8个月比4.2个月,HR=1.58,95%CI:1.00~2.51,P<0.05)。在ECP通路各基因中,RB1基因突变对全部患者预后作用显著,且在ECP突变组患者中,RB1负性预后作用显著,与ECP未突变组患者比较,mOS缩短(6.9个月比12.6个月,HR=3.14,95%CI:1.10~8.97,P=0.024)。ECP通路基因处于主克隆突变患者10例,较亚克隆突变15例患者mPFS缩短,1.3个月比5.3个月(HR=3.23,95%CI:1.25~8.37,P=0.011)。结论接受免疫治疗的老年非小细胞肺癌患者ECP通路基因突变为负性预后因子,且突变位于主克隆对预后影响更强。Objective To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status,patients were divided into an ECP pathway-related gene mutation group(ECP mutation group,n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group,n=81).The primary endpoints were overall survival(OS)and progression-free survival(PFS).Differences in survival and efficacy between the two groups were compared,and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient,and differences in survival were compared.Results Survival outcomes were worse in the ECP(+)group than in the ECP(-)group(mOS:10.9 months vs.17.1 months,HR=1.84,95%CI:1.09-3.08,P<0.05;mPFS:2.8 months vs.4.2 months,HR=1.58,95%CI:1.00-2.51,P<0.05).Of all mutations in ECP pathway-related genes,mutations in the RB1 gene had a significant prognostic effect on all patients,with the negative prognostic effect especially prominent in ECP(+)patients.Compared with ECP(-)patients,ECP(+)patients had a shorter mOS(6.9 months vs.12.6 months,HR=3.14,95%CI:1.10-8.97,P=0.024).Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months,HR=3.23,95%CI:1.25-8.37,P=0.011).Conclusions Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy,and mutations located in the clonal cluster have a stronger impact on the prognosis.

关 键 词：癌 非小细胞肺 上皮细胞 免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]