SWI/SNF复合体不同亚基突变晚期非小细胞肺癌的预后及免疫标志物分析

The Prognosis of Mutation of SWI/SNF Complex Subunits and the Relationship With Immune Markers in Advanced Non⁃Small Cell Lung Cancer

目的探讨SWI/SNF复合体(SWItch/Sucrose Non⁃Fermentable complex)不同亚基突变与晚期非小细胞肺癌(non⁃small cell lung cancer,NSCLC)的预后及与肿瘤细胞程序性死亡配体1(programmed death ligand 1,PD⁃L1)和肿瘤突变负荷(tumor mutation burden,TMB)表达的相关性。方法回顾性收集2019年4月至2020年9月在广东省人民医院确诊为不可切除局部晚期或转移性NSCLC患者,采用二代测序的方法检测ARID1A、ARID1B、SMARCA4、PBRM1、ARID2、SMARCB1、SMARCE1基因突变并计算样本TMB,免疫组化方法检测PD⁃L1的表达,结合患者的临床资料进行临床病理特征及生存分析。结果在66例患者中,10例患者检测到同时存在2个亚基共突变,共突变率达15.2%;12例患者检测到SWI/SNF复合体亚基突变伴随KRAS突变,共突变率达18.2%。ARID1A、ARID1B、SMARCA4、PBRM1、ARID2、SMARCB1、SMARCE1亚基突变各占24%、12%、34%、12%、16%、1%、1%。SWI/SNF复合体亚基突变的NSCLC患者PD⁃L1≥1%占83.7%,其中ARID1A和SMARCA4突变患者PD⁃L1≥1%均占22.4%;各亚基突变的TMB具有统计学差异(P=0.01),其中SMARCA4突变患者TMB≥10 Muts/Mb占24.2%。生存分析结果显示SWI/SNF复合体不同亚基突变之间的总生存时间差异无统计学意义(P=0.61)。结论SWI/SNF复合体不同亚基突变在NSCLC中的预后无明显差异,但SMARCA4突变倾向于伴随更高的TMB,其潜在的临床意义有待进一步研究。

Objective This study was designed to explore the prognosis of SWItch/Sucrose Non-Fermentable complex(SWI/SNF)complex subunits mutation and the relation with tumor programmed death ligand 1(PD-L1)and tumor mutation burden(TMB)in unresectable locally advanced or metastatic non-small cell lung cancer. Methods Patients diagnosed with unresectable locally advanced or metastatic non-small cell lung cancer from April 2019 to September 2020in the Guangdong Provincial People’s Hospital were retrospectively collected. Next-generation sequencing(NGS)was used to detect ARID1A,ARID1B,SMARCA4,PBRM1,ARID2,SMARCB1,and SMARCE1 genomic alterations,TMB was calculated simultaneously,the expression of PD-L1 was detected through immunohistochemistry,and clinicopathological characteristics and survival analysis were carried out in combination with the clinical data of the patients. Results 15.2%(10/66)of patients were found to have two subunits mutation simultaneously;12 patients(18.2%)were detected with SWI/SNF complex subunit mutations accompanied by KRAS mutation. ARID1A,ARID1B,SMARCA4,PBRM1,ARID2,SMARCB1,and SMARCE1 subunit mutation accounted for 24%,12%,34%,12%,16%,1%,and 1%,respectively.83.7% of patients with SWI/SNF complex subunit mutation expressed PD-L1 ≥ 1%,and the expression of PD-L1≥1%accounted for 22.4% with ARID1A and SMARCA4 mutation,respectively;There was a significant difference in tumor mutation burden(TMB)between SWI/SNF complex subunits(P=0.01),among which mutation of SMARCA4 accounted for 24.2% when TMB≥ 10 Muts/Mb. Survival analysis showed no significant difference in overall survival among different subunit mutations of the SWI/SNF complex(P=0.61). Conclusions There was no significant prognostic of survival between different mutational SWI/SNF subunits in unresectable locally advanced or metastatic NSCLC. But patients with SMARCA4 mutation tended to be higher TMB than others, which needs further investigation for its potential clinical value for immune therapy.