晚期非小细胞肺癌患者骨转移灶与内脏病灶的全身药物治疗反应差异分析

Differences in response to systemic drug therapy between bone metastases and visceral lesions in advanced non-small cell lung cancer

目的探究晚期非小细胞肺癌患者骨转移灶与内脏病灶对全身药物治疗的反应差异,探索临床特征及基因表达层面可能引起差异的相关因素。方法本研究收集2010年1月至2020年12月,我院骨肿瘤科就诊的非小细胞肺癌骨转移患者的临床资料。通过分析全身药物治疗后骨转移灶及内脏病灶进展情况,从而反映病灶对全身药物治疗的反应性,并用GEO(gene expression omnibus)数据库中GSE76194骨转移灶与原发灶的基因表达数据进行验证。结果骨转移灶与内脏病灶全身药物治疗后,优先进展率分别为79.7%以及20.3%(P<0.05),Logistic回归分析结果显示表皮生长因子受体(epidermal growth factor receptor,EGFR)突变状态(OR=6.76,P=0.009)以及药物治疗前内脏转移部位(OR=0.078,P=0.001)是影响治疗反应差异的独立因素,Cox回归分析结果显示有吸烟史(HR=4.4,P=0.0027)、仅使用靶向药物(HR=2.94,P=0.0055)以及全身药物治疗前内脏转移部位(HR=0.37,P=0.011)是影响骨转移灶优先进展的独立预后因素,基因表达数据分析共筛选出938个差异表达基因,通过差异基因的GSEA分析显著富集到4条耐药相关通路。结论晚期非小细胞肺癌患者骨转移灶与内脏病灶对全身药物治疗反应存在差异,骨转移灶存在耐药相关通路的表达上调,伴有EGFR突变的患者骨转移灶较腹腔外内脏病灶对全身药物治疗反应性更差,建议对全身药物治疗反应性差的非小细胞肺癌骨转移患者积极采取局部治疗。

Objective Systemic drug therapy(SDT)plays a crucial role in the control of advanced non-small cell lung cancer(NSCLC).This study aims to explore the differences in response to systemic drug therapy between bone metastases and visceral lesions in patients with advanced NSCLC and the relevant factors in clinical characteristics and gene expression.Methods This study collected clinical data of patients with bone metastases treated by NSCLC in the Musculoskeletal Tumor Center,Peking University People's Hospital,from January 2010to December 2020.Differences in the progression of bone metastases and visceral lesions after SDT reflected the responsiveness of the lesions to SDT.The differences were validated using gene expression data from GSE76194bone metastases and primary lesions in the Gene Expression Omnibus(GEO)database.Results The optimal rate of progression of bone metastases and visceral lesions after systemic drug treatment was 79.7% and 20.3%,respectively(P<0.05).The results of logistic regression analysis showed that the mutation status of epidermal growth factor receptor(EGFR)(OR=6.76,P=0.009)and the location of visceral metastases before drug treatment(OR=0.078,P=0.001)were independent factors affecting the difference in treatment response.Cox regression analysis showed that a history of smoking(HR=4.4,P=0.0027),using targeted drugs only(HR=2.94,P=0.0055),the location of visceral metastases before systemic drug treatment(HR=0.37,P=0.011)were independent prognostic factors affecting the priority progression of bone metastases.Gene expression data analysis screened 938 differentially expressed genes,and GSEA analysis of the differentially expressed genes significantly enriched four drug resistancerelated pathways.Conclusions In patients with advanced NSCLC,there are significant differences in response to systemic drug therapy between bone metastases and visceral lesions.There is an upregulation of drug resistance-related pathways in bone metastases.Bone metastases in patients with EGFR mutations have a poorer response to SDT than extraperitoneal visceral lesions.It is recommended to actively take local treatment for bone metastases with poor response to SDT in advanced NSCLC.