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Abstract：
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.
摘要：
肺癌是发病率和死亡率最高的恶性肿瘤之一。小细胞肺癌(SCLC)是肺癌中恶性程度最高的病理类型,转移早,预后差。目前,缺乏预测SCLC患者预后的有效指标。Delta-like3蛋白(DLL3)在SCLC表面选择性表达,并参与增殖和侵袭。神经元特异性烯醇化酶（NSE）是一种烯醇化酶同工酶，通常被认为是SCLC的生物标志物，可能与SCLC的分期相关。预后和化疗反应。NSE可以受到不同类型因素的影响。探讨DLL3在肿瘤组织中的表达水平与铂/依托泊苷化疗反应的关系。并评估DLL3，NSE和其他潜在预后因素在晚期SCLC患者中的预后价值。2014年至2020年在中大医院诊断为SCLC的97例患者被纳入研究。在任何处理之前使用ELISA方法测试血清NSE水平。免疫组化(IHC)法检测肿瘤组织中DLL3的表达。我们研究了DLL3表达与化疗和生存率的关系。通过Kaplan-Meier方法估计无进展生存期(PFS)和总生存期(OS)。多变量Cox比例风险回归用于确定PFS和OS的预测因子。通过IHC在所有患者的84.5%（82/97）的肿瘤样本中检测到DLL3，主要位于SCLC细胞表面。较低的DLL3表达与较长的PFS和较好的化疗反应相关。OS无显著差异。CoxHazard模型的多变量分析表明,高DLL3表达和最大肿瘤大小>5cm是PFS的独立危险因素，其中NSE<35ng/mL和年龄<70岁是OS的独立预后因素。早期是影响PFS和OS的独立预后因素(P<0.05log-rank)。DLL3在大多数SCLC中表达。肿瘤中DLL3表达水平和血清中NSE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。
