SMARCA4缺失型胸部未分化肿瘤的临床特征及预后分析

Clinical characteristics and prognostic analysis of thoracic SMARCA4-deficient undifferentiated tumor

目的总结分析SMARCA4缺失型胸部未分化肿瘤(SMARCA4-UT)的临床特征及预后。方法回顾性分析2018年1月至2023年12月郑州大学第一附属医院确诊的51例SMARCA4-UT患者的临床资料,以同期收治的52例SMARCA4表达完整的非小细胞肺癌(SMARCA4-iNSCLC)患者作为对照。应用Kaplan-Meier生存分析及log-rank检验比较两组患者生存差异,Cox回归模型探讨影响两组患者预后的因素。结果SMARCA4-UT组中男50例,女1例,年龄(63.8±9.7)岁。与SMARCA4-iNSCLC组相比,SMARCA4-UT组男性及吸烟者占比更高,Ki-67更高(均P<0.05)。SMARCA4-UT以实性病灶为主、黏附性差,部分呈横纹肌样形态。免疫组化方面,BRG1均为阴性,甲状腺转录因子-1、P40、新天冬氨酸蛋白酶A等大多为阴性,部分婆罗双树样基因4阳性。Ki-67≥30%者较多(47/51,92%)。SMARCA4-UT组中10例患者完善二代测序基因检测,6例发现SMARCA4突变,常合并TP53突变(8/10,80%)、STK11突变(3/10,30%)、KRAS突变(2/10,20%),常见驱动基因突变较少,平均肿瘤突变负荷为16.12个突变/Mb。与SMARCA4-iNSCLC组相比,SMARCA4-UT组中位总生存期(OS)更短(12个月比45个月,P<0.001);在Ⅲ~Ⅳ期SMARCA4-UT患者中,使用免疫治疗的患者比未使用免疫治疗中位OS更长(23个月比7个月,P=0.027)。多因素Cox回归模型分析结果显示,SMARCA4缺失是SMARCA4-UT及SMARCA4-iNSCLC患者预后的危险因素[HR=7.954(95%CI:2.764~22.890),P<0.001]。结论SMARCA4-UT是一种少见的不同于SMARCA4-iNSCLC的未分化肿瘤,常见于老年吸烟男性,具有侵袭性高、预后差等特点,典型的病理特征是BRG1阴性。免疫治疗有一定的疗效。

Objective To summarize and analyze the clinical characteristics and prognosis of thoracic SMARCA4-deficient undifferentiated tumor(SMARCA4-UT).Methods A retrospective analysis was conducted on the clinical data of 51 patients with SMARCA4-UT who were diagnosed in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023,and 52 patients with SMARCA4-intact non-small cell lung cancer(SMARCA4-iNSCLC)expression admitted during the same period were used as controls.The Kaplan-Meier survival analysis and log-rank test were used to analyze the survival difference between the two groups of patients,and the Cox regression model was used to explore the factors influencing the prognosis of the two groups of patients.Results In the SMARCA4-UT group,there were 50 males and 1 female,with the age of(63.8±9.7)years.Compared to the SMARCA4-iNSCLC group,the SMARCA4-UT group exhibited a higher proportion of male patients and smokers,as well as a higher Ki-67 level(all P<0.05).SMARCA4-UT is mainly characterized by solid lesions with poor adhesion,and some of them exhibit rhabdomyoid morphology.Immunohistochemistry revealed negative results for BRG1,thyroid transcription factor-1,P40,NapsinA,and others were mostly negative,while some patients were positive for spalt-like transcription factor 4.There were a relatively large number of cases with Ki-67≥30%(47/51,92%).Among the 10 patients in the SMARCA4-UT group who underwent next-generation sequencing genetic testing,6 patients were found to have SMARCA4 mutations,often accompanied by TP53(8/10,80%),STK 11(3/10,30%),KRAS(2/10,20%),with fewer common driver gene mutations.The average tumor mutation burden was 16.12 mutations/Mb.Compared with SMARCA4-iNSCLC patients,the median overall survival of SMARCA4-UT patients was significantly shorter(12 months vs 45 months,P<0.001),and the median overall survival of patients with stageⅢ-ⅣSMARCA4-UT treated with immunotherapy was longer than that of patients without immunotherapy(23 months vs 7 months,P=0.027).The results of the multivariate Cox regression model analysis indicated that SMARCA4 deficiency is a risk factor for prognosis in patients with SMARCA4-UT and SMARCA4-iNSCLC[HR=7.954(95%CI:2.764-22.890),P<0.001].Conclusions SMARCA4-UT is a rare undifferentiated tumour distinct from SMARCA4-iNSCLC,which is prevalent among elderly male smokers.It possesses high invasiveness and poor prognosis.The typical pathological characteristic is negative BRG1.Immunotherapy demonstrates a certain effect.