循环白介素-33 水平与肺癌的进展相关。

Circulating IL-33 level is associated with the progression of lung cancer.

机构信息

Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi-Si, Gyeongsangbuk-Do, Republic of Korea.

Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea.

出版信息

Lung Cancer. 2015 Nov;90(2):346-51. doi: 10.1016/j.lungcan.2015.08.011. Epub 2015 Aug 20.

DOI:10.1016/j.lungcan.2015.08.011

PMID:26342550

Abstract

OBJECTIVES

Interleukin (IL)-33 protects against infection and inflammation; however, few studies have explored the relevance of IL-33 in lung cancer patients. We evaluated relation of plasma IL-33 levels with development and progression of lung cancer.

MATERIALS AND METHODS

A total of 160 patients with lung cancer and 160 controls with normal lungs were enrolled. Plasma IL-33 levels were measured using a specific sandwich ELISA; these levels were followed-up in 18 patients who underwent surgery and in 14 patients treated with chemotherapy. Malignant lesions and normal lung tissues from 10 cancer patients were subjected to immunohistochemical staining for IL-33.

RESULTS

IL-33 levels were significantly lower in cancer patients than normal controls (0.08 vs. 0.38 ng/mL, p=0.005). Among cancer patients, IL-33 decreased in a stage-dependent manner from 0.76 ng/mL in stage I patients to 0.25 ng/mL in those with stage II, 0.08 ng/mL in those with stage III, and 0.08 ng/mL in those with stage IV (p=0.002). The levels were higher at stage I (p=0.041) and markedly lower at stages III and IV than those of controls (p=0.005 and p=0.001, respectively). A similar pattern was observed when IL-33 levels were analyzed by T stage; the levels were 0.39 ng/mL at T1/T2 vs. 0.08 ng/mL at T3/T4 (p=0.001). However, no difference was noted when stage N1 levels were compared with N2 and N3 levels (p=0.058), or between stage M0 and M1 levels (p=0.147). IL-33 levels gradually decreased after surgical resection of malignant lesions (from 1.075 to 0.756 ng/mL, p=0.006), but were unchanged after chemotherapy (0.705 vs. 0.829 ng/mL, p=0.875). On immunohistochemical staining, bronchial epithelial and vascular endothelial cells of normal lung tissues mainly expressed IL-33.

CONCLUSIONS

Plasma IL-33 levels are associated inversely with progression of lung cancer. The observed decreases may be attributed to lung volume reduction containing bronchial epithelium and vascular endothelium as the sources of IL-33.

摘要

目的

白细胞介素 (IL)-33 可预防感染和炎症；然而，很少有研究探讨 IL-33 与肺癌患者的相关性。我们评估了血浆 IL-33 水平与肺癌的发生和发展的关系。

材料与方法

共纳入 160 例肺癌患者和 160 例肺部正常的对照者。采用特异性夹心 ELISA 法测定血浆 IL-33 水平；对 18 例行手术治疗的患者和 14 例行化疗的患者进行了随访。对 10 例癌症患者的恶性病变和正常肺组织进行 IL-33 免疫组织化学染色。

结果

癌症患者的 IL-33 水平明显低于对照者（0.08 vs. 0.38 ng/mL，p=0.005）。在癌症患者中，IL-33 水平呈阶段依赖性降低，从 I 期患者的 0.76 ng/mL 降至 II 期患者的 0.25 ng/mL、III 期患者的 0.08 ng/mL 和 IV 期患者的 0.08 ng/mL（p=0.002）。I 期患者的水平较高（p=0.041），III 期和 IV 期患者的水平明显低于对照者（p=0.005 和 p=0.001）。当按 T 分期分析 IL-33 水平时，也观察到类似的模式；T1/T2 患者为 0.39 ng/mL，而 T3/T4 患者为 0.08 ng/mL（p=0.001）。然而，N1 期与 N2 和 N3 期相比（p=0.058），或 M0 期与 M1 期相比（p=0.147），其水平无差异。恶性病变切除后，IL-33 水平逐渐下降（从 1.075 降至 0.756 ng/mL，p=0.006），但化疗后无变化（0.705 与 0.829 ng/mL，p=0.875）。免疫组织化学染色显示，正常肺组织的支气管上皮细胞和血管内皮细胞主要表达 IL-33。