Department of Clinical Laboratory, Liyang People's Hospital, Liyang, China.
Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
J Clin Lab Anal. 2022 Feb;36(2):e24224. doi: 10.1002/jcla.24224. Epub 2022 Jan 12.
Immunotherapy was widely used for the treatment of non-small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.
Serum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta-Plex Human Immuno-Oncology Checkpoint Panel.
The expression levels of sTIM-3, sCD137, sCD27, sLAG-3, sIDO, sPD-L2, sCD152, sCD80, and sPD-1 were all significantly increased in serum of NSCLC patients. Especially, sLAG-3 was significantly elevated in serum of NSCLC patients at early-stage (stages I and II), TIM-3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early-stage groups. Receiver operating characteristics (ROC) results showed that except for PD-1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM-3 had the highest diagnostic accuracy, followed by sLAG-3. Combining sTIM-3, sLAG-3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM-3 and sIDO were correlated with stage and age, respectively.
TIM-3 and LAG-3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM-3, LAG-3, and CD137 could increase the diagnostic accuracy.
免疫疗法已广泛应用于非小细胞肺癌（NSCLC）的治疗。然而，单独或同时抑制免疫检查点是否能提高 NSCLC 的治疗效果仍有待研究。在这里，我们研究了几种检查点的异常水平，并评估了它们对 NSCLC 的潜在诊断价值。
收集 2019 年 11 月至 2020 年 7 月期间南京鼓楼医院 89 例 NSCLC 患者和 57 例健康供者的血清样本。通过 Procarta-Plex Human Immuno-Oncology Checkpoint Panel 定量检测 14 个人类免疫检查点。
NSCLC 患者血清中 sTIM-3、sCD137、sCD27、sLAG-3、sIDO、sPD-L2、sCD152、sCD80 和 sPD-1 的表达水平均显著升高。特别是，早期（I 期和 II 期）NSCLC 患者血清中 sLAG-3 显著升高，晚期（III 期和 IV 期）NSCLC 患者的 TIM-3、CD137 和 CD27 水平明显高于早期组。受试者工作特征（ROC）结果表明，除 PD-1 外，所有其他免疫检查点蛋白对 NSCLC 均具有潜在的诊断价值。sTIM-3 具有最高的诊断准确性，其次是 sLAG-3。联合检测 sTIM-3、sLAG-3 和 sCD137 可提高诊断准确性。此外，sCD27 与 NSCLC 癌症类型、年龄、性别和疾病分期相关，而 sCD137 与年龄和疾病分期相关。sTIM-3 和 sIDO 分别与分期和年龄相关。
TIM-3 和 LAG-3 是 NSCLC 早期诊断的独立生物标志物。联合检测 TIM-3、LAG-3 和 CD137 可提高诊断准确性。
