Department of Respiratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Respiratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Medicine (Baltimore). 2024 Jun 7;103(23):e38487. doi: 10.1097/MD.0000000000038487.
Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.
肺癌是发病率和死亡率增长最快，对人群健康和生命威胁最大的恶性肿瘤之一。小细胞肺癌（SCLC）是肺癌中最恶性的病理类型，具有早期转移和预后不良的特点。目前，缺乏有效的指标来预测 SCLC 患者的预后。Delta-like 3 蛋白（DLL3）在 SCLC 表面选择性表达，参与增殖和侵袭。神经元特异性烯醇化酶（NSE）是烯醇化酶同工酶，一般被认为是 SCLC 的标志物，可能与 SCLC 的分期、预后和化疗反应相关。NSE 会受到不同类型因素的影响。本研究旨在探讨肿瘤组织中 DLL3 表达水平与铂类/依托泊苷化疗反应的关系，并评估 DLL3、NSE 及其他潜在预后因素在晚期 SCLC 患者中的预后价值。
2014 年至 2020 年，我们在中大医院共纳入 97 例经组织学或细胞学确诊为 SCLC 的患者。所有患者在接受任何治疗前均采用酶联免疫吸附法（ELISA）检测血清 NSE 水平。采用免疫组化（IHC）方法检测肿瘤组织中 DLL3 的表达。我们探讨了 DLL3 表达与化疗和生存的关系。采用 Kaplan-Meier 法估计无进展生存期（PFS）和总生存期（OS）。采用多变量 Cox 比例风险回归分析确定 PFS 和 OS 的预测因素。
通过 IHC 检测，在 84.5%（82/97）的患者肿瘤标本中检测到 DLL3，主要位于 SCLC 细胞表面。较低的 DLL3 表达与更长的 PFS 和更好的化疗反应相关。OS 无显著差异。多因素 Cox 风险模型分析显示，高 DLL3 表达和最大肿瘤直径＞5cm 是 PFS 的独立危险因素，而 NSE＜35ng/ml 和年龄＜70 岁是 OS 的独立预后因素。早期是 PFS 和 OS 的独立预后因素（P＜.05log-rank）。DLL3 在大多数 SCLC 中表达。肿瘤中 DLL3 的表达水平和血清中 NSE 的水平可能是预测 SCLC 预后的有用生物标志物。DLL3 可能是未来 SCLC 的潜在治疗靶点。
