Li Wei, Ye Lingyun, Huang Yan, Zhou Fei, Wu Chunyan, Wu Fengying, He Yayi, Li Xuefei, Wang Haowei, Xiong Anwen, Gao Guanghui, Wang Lei, Su Chunxia, Ren Shengxiang, Chen Xiaoxia, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Lung Cancer. 2022 May;167:25-33. doi: 10.1016/j.lungcan.2022.03.019. Epub 2022 Mar 29.
To explore the characteristics of Notch pathway in small cell lung cancer (SCLC), clarify the expression of delta-like protein 3 (DLL3) in SCLC patients undergoing surgical treatment, and explore the correlation between DLL3 expression and clinicopathological features, prognosis, and immune microenvironment.
A total of 134 patients who received surgical treatment and were diagnosed as SCLC by postoperative histopathology were enrolled. All exon gene sequencing was performed in tumor tissues and adjacent normal tissues of 28 patients to clarify the genomic characteristics of SCLC. The expressions of DLL3 and programmed cell death 1 ligand 1 (PDL1) were detected by immunohistochemistry (IHC) in 101 postoperative pathological specimens.
Notch receptor mutations are common, but the overall mutation rate of Notch ligand family is not high and mutually exclusive. The mutation status of Notch and Notch1 gene were not related to the prognosis. Notch1 gene mutation was significantly negatively correlated with the expression of PD-L1. DLL3 was highly expressed in SCLC and had no significant correlation with prognosis. There was a positive correlation between DLL3 expression and PD-L1 expression. Patients with positive DLL3 expression and no NOTCH 1 gene mutation had higher PD-L1 expression. SCLC patients with such characteristics may be more likely to benefit from immunotherapy.
This study preliminarily explored the genomic characteristics and immune microenvironment of surgical resection of SCLC in China, and found the correlation between Notch gene mutation, DLL3 expression and PD-L1 expression, which provided a new idea for selecting appropriate treatment strategies for SCLC in the future.
探讨Notch通路在小细胞肺癌（SCLC）中的特征，明确接受手术治疗的SCLC患者中Delta样蛋白3（DLL3）的表达情况，并探讨DLL3表达与临床病理特征、预后及免疫微环境之间的相关性。
纳入134例接受手术治疗且术后组织病理学诊断为SCLC的患者。对28例患者的肿瘤组织及癌旁正常组织进行全外显子基因测序，以明确SCLC的基因组特征。采用免疫组织化学（IHC）法检测101例术后病理标本中DLL3和程序性细胞死亡1配体1（PDL1）的表达。
Notch受体突变常见，但Notch配体家族的总体突变率不高且相互排斥。Notch和Notch1基因的突变状态与预后无关。Notch1基因突变与PD-L1的表达呈显著负相关。DLL3在SCLC中高表达，与预后无显著相关性。DLL3表达与PD-L1表达呈正相关。DLL3表达阳性且无NOTCH 1基因突变的患者PD-L1表达较高。具有此类特征的SCLC患者可能更易从免疫治疗中获益。
本研究初步探讨了我国SCLC手术切除的基因组特征及免疫微环境，发现了Notch基因突变、DLL3表达与PD-L1表达之间的相关性，为未来SCLC选择合适的治疗策略提供了新思路。
