巨噬细胞抑制因子1 在非小细胞肺癌诊断 及靶向治疗疗效预测中的临床价值

Clinical significance of MIC-1 in non-small cell lung cancer

摘要:

目的 探讨巨噬细胞抑制因子1（MIC-1）在非小细胞肺癌（NSCLC）诊断及靶向治疗疗效预测 中的应用价值。方法 选取2013 年1 月-2015 年1 月该院收治的Ⅲ b 期、Ⅳ期NSCLC 患者94 例、肺部良性疾 病78 例及体检健康者70 例分别作为NSCLC 组、良性组及对照组，采用双抗体夹心酶联免疫吸附实验检测 MIC-1 水平。NSCLC 组均接受靶向治疗，单因素和多因素Cox 回归分析NSCLC 组中位生存时间的影响因素。 结果 NSCLC 组血清MIC-1 水平高于良性组和对照组，且良性组高于对照组（P <0.05）；NSCLC 组不同 TNM 分期的MIC-1 水平比较，差异有统计学意义（P <0.05），不同年龄、性别、靶向治疗方案及表皮生长 因子受体（EGFR）基因突变的比较，差异无统计学意义（P >0.05）。NSCLC 组均接受靶向治疗，治疗3 和5 个月MIC-1 水平均较治疗前和治疗1 个月降低（P <0.05）；治疗前，治疗1、3 及5 个月组间比较，差异有统 计学意义（P <0.05）；治疗5 个月时，治疗有效率32.98% ；Kaplan-Meier 法估计生存率，NSCLC 组中位生存 时间（MST）为17.9 个月。以1 390 pg/ml 为临界值，将其分为MIC-1 ≤ 1 390 pg/ml 组（59 例）和MIC- 1>1 390 pg/ml 组（35 例），两组3 年生存率分别为33.90% 和14.29%（P <0.05）。Cox 回归分析显示，TNM 分期、 EGFR 基因突变及MIC-1 水平是影响NSCLC 组MST 的危险因素。结论 血清MIC-1 水平与Ⅲ b 期、Ⅳ期 NSCLC 组TNM 分期和靶向治疗效果有关，可用于预测患者预后。

Abstract:

Objective To investigate the clinical significance of macrophage inhibitory cytokine-1 (MIC- 1) in non-small cell lung cancer (NSCLC). Methods A total of 94 patients with stage Ⅲ band stage Ⅳ NSCLC, 78 patients with benign pulmonary diseases, and 70 healthy subjects admitted to the hospital from January 2013 to January 2015 were included in this study. The MIC-1 level was detected by ELISA. Patients with NSCLC received targeted therapy. Results Serum level of MIC-1 was higher significantly in the NSCLC group compared with benign group and control group, while MIC-1 was upregulated in the benign group compared with control group (P < 0.05). MIC-1 was closely associated with TNM stages (P < 0.05) while no significant relationship was observed among age, gender, targeted therapy and EGFR gene mutation in NSCLCgroup (P > 0.05). MIC-1 levels in patients receiving treatments for 3 months and 5 months decreased compared with those before treatment and receiving treatment for 1 month (P < 0.05). There were significant differences in MIC-1 levels between groups at 3 months, 5 months and 7 months prior to treatment (P < 0.05). Treatment effective rate was 32.98% with 5 months of treatments. The treatment effective rate in patients with mutation was higher than that of wild type (64.86% vs 12.28%, P < 0.05). The MIC-1 level in treatment group with positive response was significantly lower than that in group with negative response (P < 0.05). ROC analysis showed that the median survival time (MST) was 17.9 months. With 1,390 pg/ml as the cut-off value, patients were divided into the low group (MIC-1 ≤ 1,390 pg/ml group, n = 59) and high group (MIC-1 > 1,390 pg/ml group, n = 35). Patients in high group experienced significant higher 3-year survival rate compared to low group (33.90% vs 14.29%, P < 0.05). Cox analysis showed that TNM stage, EGFR gene mutation and MIC-1 level were independent risk factors for MST of patients with NSCLC. Conclusion The serum MIC-1 level is correlated to TNM stages, and the effectiveness of targeted therapy, and MIC-1 may be a prognostic biomarker in patients with stage Ⅲ b-stage Ⅳ NSCLC