非小细胞肺癌程序性死亡配体-1表达与临床病理特征和常见驱动基因变异的相关性研究

The correlation between the expression of programmed death ligand 1 in non-small cell lung cancer and clinical pathological features and common driver gene mutation

目的分析非小细胞肺癌(NSCLC)患者程序性死亡配体-1(PD-L1)表达与临床病理特征和常见驱动基因变异的相关性,为NSCLC患者免疫治疗提供理论依据。方法回顾性纳入首都医科大学附属北京胸科医院病理科2018年1月—2021年12月进行PD-L1免疫组织化学染色及EGFR、KRAS、ALK、ROS1、BRAF、RET、MET和HER2基因检测的NSCLC患者,分析不同病理特征与不同驱动基因变异对NSCLC患者PD-L1蛋白表达的影响。结果PD-L1蛋白表达检测2386例,阳性率为45.8%(1093/2386),其中低表达组(1%≤TPS≤49%)为62.0%(678/1093),高表达组(TPS≥50%)为38.0%(415/1093),不同临床病理特征PD-L1表达存在差异。多因素logistic回归分析显示吸烟史、淋巴结转移、病理亚型、EGFR突变、KRAS突变、ALK和MET突变是NSCLC患者PD-L1是否表达的独立危险因素(P<0.05),淋巴结转移和EGFR突变是NSCLC患者PD-L1表达水平的独立危险因素(P<0.05)。结论PD-L1蛋白在吸烟、鳞癌、KRAS突变型、ALK阳性和MET突变型患者中阳性率高,在淋巴结转移和EGFR野生型患者中高表达。区别于EGFR阳性的NSCLC患者,KRAS、MET阳性的NSCLC患者有望从免疫检查点抑制剂治疗中获益。

Objective The aim of this study was to analyze the correlation between the expression of programmed death ligand 1(PD-L1)and clinical pathological features and common driver gene mutation in patients with non-small cell lung cancer(NSCLC),so as to provide theoretical basis for immunotherapy of NSCLC patients.Methods Retrospective inclusion of NSCLC patients who underwent PD-L1 immunohistochemistry staining and epidermal growth factor receptor(EGFR),Kirsten rat sarcoma viral oncogene(KRAS),anaplastic lymphoma kinase(ALK),RET proto-oncogene(RET),v-Raf murine sarcoma viral oncogene homolog(BRAF),ROS proto-oncogene 1(ROS1),human epidermal growth factor receptor-2(HER2),cellular-mesenchymal to epithelial transition factor(MET)gene testing from the Pathology Department of Beijing Thoracic Hospital Affiliated to Capital Medical University from January 2018 to December 2021.Analysis of the impact of different pathological features and driver gene variants on PD-L1 protein expression in NSCLC patients.Results PD-L1 protein expression was detected in 2386 cases,with a positive rate of 45.8%(1093/2386).Among them,the low expression group(1%≤TPS≤49%)was 62.0%(678/1093),while the high expression group(TPS≥50%)was 38.0%(415/1093).There were differences in PD-L1 expression among different clinical and pathological features.Multivariate logistic regression analysis showed that smoking history,lymph node metastasis,pathological subtypes,EGFR mutations,KRAS mutations,ALK and MET mutations were independent risk factors for PD-L1 expression in NSCLC patients(P<0.05),while lymph node metastasis and EGFR mutations were independent risk factors for PD-L1 expression levels in NSCLC patients(P<0.05).Conclusion The PD-L1 protein has a high positive rate in patients with smoking,squamous cell carcinoma,KRAS mutant,ALK positive,and MET mutant,and is highly expressed in patients with lymph node metastasis and EGFR wild-type.Different from NSCLC patients with EGFR positive,NSCLC patients with KRAS,and MET positive are expected to benefit from the treatment of immune checkpoint inhibitors.