2024 年第 12 期 第 0 卷

神经元特异性烯醇化酶水平与信迪利单抗联合含铂双药化疗治疗晚期小细胞肺癌效果的关系

Relationship between the level of neuron-specific enolase and the effect of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced small cell lung cancer

作者：张大灿黄彩仪黄东毅

英文作者：Zhang Dacan Huang Caiyi Huang Dongyi

单位：南方医科大学珠江医院药学部，广州510330

英文单位：Department of Pharmacy Zhujiang Hospital Southern Medical University Guangzhou 510330 China

关键词：小细胞肺癌；神经元特异性烯醇化酶；信迪利单抗；含铂双药化疗

英文关键词：Smallcelllungcancer;Neuronspecificenolase;Sintilimab;Platinum-baseddoublet-chemotherapy

• 摘要：

• 目的 探究神经元特异性烯醇化酶（NSE）水平与信迪利单抗联合含铂双药化疗治疗晚期小细胞肺癌（SCLC）效果的关系。方法 回顾性分析2022年2月至2024年2月于南方医科大学珠江医院就诊并采用信迪利单抗联合含铂双药化疗的108例晚期SCLC患者临床资料，根据临床疗效分为有效组（66例）和无效组（42例）。比较2组患者临床资料、T细胞亚群、免疫球蛋白（Ig）、胃泌素释放肽前体（Pro-GRP）、NSE水平。多因素Logistic回归分析治疗无效的独立危险因素，同时分析NSE水平与信迪利单抗联合含铂双药化疗治疗晚期SCLC无效风险的独立相关性，并使用E值法进行敏感性分析。建立限制性立方样条（RCS）模型分析血清NSE水平与信迪利单抗联合含铂双药化疗治疗晚期SCLC无效风险的关联强度的剂量-反应关系。结果 2组患者吸烟史、肿瘤分期、CD+3、CD+4、CD+8、IgA、IgG、IgM和Pro-GRP水平比较差异均有统计学意义（均P＜0.05）。2组患者第1、2、3、4次化疗后NSE水平以及ΔNSE1、ΔNSE2、ΔNSE3和ΔNSE4水平差异均有统计学意义（均P＜0.05），同组间每次化疗后，较上一次化疗相比，NSE水平差异均有统计学意义（均P＜0.05）。分层回归分析结果显示，CD+3、CD+4和CD+8对NSE水平产生显著的正向影响（均P＜0.05），IgA和IgM对NSE水平产生显著的正向影响（均P＜0.05）。校正吸烟史、肿瘤分期、Pro-GRP后，NSE水平仍是信迪利单抗联合含铂双药化疗治疗晚期SCLC无效的独立危险因素，存在独立相关性（比值比=2.620，95%置信区间：1.538～4.580，P＜0.001）。且NSE从低到高五分位数组趋势性检验存在统计学意义（P趋势＜0.001）。敏感性分析显示E值=2.619。RCS模型分析结果显示，NSE水平与信迪利单抗联合含铂双药化疗治疗晚期SCLC无效风险的关联强度呈线性剂量-反应关系（P非线性=0.195）。亚组分析结果显示，在不同肿瘤分期、Pro-GRP、CD+3、CD+4、CD+8、IgA、IgG和IgM水平患者中，NSE与信迪利单抗联合含铂双药化疗治疗晚期SCLC无效风险的相关性稳定存在，且亚组间不存在交互作用（均P交互＞0.05）。结论 NSE水平可显著影响信迪利单抗联合含铂双药化疗治疗晚期SCLC的临床效果，NSE水平降低的患者临床疗效改善。

• Objective To investigate the relationship between neuron-specific enolase (NSE) level and the effect of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced small cell lung cancer (SCLC). Methods The clinical data of 108 patients with advanced SCLC treated with sintilimab combined with platinum-based doublet-chemotherapy in Zhujiang Hospital, Southern Medical University from February 2022 to February 2024 were retrospectively analyzed. According to the clinical efficacy, the patients were divided into effective group (66 cases) and ineffective group (42 cases). The clinical data, T cell subsets, immunoglobulin (Ig), pro-gastrin-releasing peptide (Pro-GRP) and NSE level were compared between the two groups. Multivariate Logistic regression was used to analyze the independent risk factors of ineffectiveness, and the independent correlation between NSE level and the ineffectiveness risk of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC was analyzed, and the sensitivity analysis was performed using the E-value method. Restricted cubic spline (RCS) model was established to analyze the dose-response relationship between serum NSE level and the ineffective risk of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC. Results There were significant differences in smoking history, tumor stage, CD+3, CD+4, CD+8, IgA, IgG, IgM, Pro-GRP level between the two groups (P＜0.05). There were significant differences in NSE level and ΔNSE1, ΔNSE2, ΔNSE3 and ΔNSE4 level after the first, second, third and fourth cycles of chemotherapy between the two groups(all P＜0.05). In the same group, the NSE level after each chemotherapy were significantly different from those after the last chemotherapy (all P＜0.05). Hierarchical regression analysis showed that CD+3, CD+4 and CD+8 had a significant positive effect on NSE level (all P＜0.05), and IgA and IgM had a significant positive effect on NSE level (both P＜0.05). After adjusting for smoking history, tumor stage and Pro-GRP, serum NSE level was still an independent risk factor for the inefficacy of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC (odds ratio=2.620, 95% confidence interval: 1.538-4.580, P＜0.001). The trend test of NSE from low to high quintile groups was statistically significant(Ptrend＜0.001), and sensitivity analysis showed that the E-value was 2.619. RCS model analysis showed that there was a linear dose-response relationship between NSE level and the inefficacy risk of sindilizumab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC (Pfor non linear=0.195). Subgroup analysis showed that the correlation between NSE and sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC was stable in patients with different tumor stages, Pro-GRP, CD+3, CD+4, CD+8, IgA, IgG and IgM level， and there was no interaction between subgroups (all Pfor interaction＞0.05). Conclusion NSE level can significantly affect the clinical efficacy of sintilimab combined with platinum-based doublet-chemotherapy in the treatment of advanced SCLC. Patients with lower NSE level have better clinical efficacy.