Background: Increased macrophage inhibitory cytokine-1 (MIC-1), member of transforming growth factor-β (TGF-β) superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC).
Methods: A total of 152 consecutive patients with stage I-II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients.
Results: The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001) and benign pulmonary disease patients (P<0.001). A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001), female (P=0.03) and T2 (P=0.022). A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL) was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%). Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035).
Conclusions: High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC. .
背景与目的 巨噬细胞抑制因子-1（macrophage inhibitory cytokine-1, MIC-1）是人转化生长因子β（transforming growth factor-β, TGF-β）超家族中重要成员，研究发现MIC-1表达水平在多种上皮来源肿瘤患者血清中均有显著升高。本研究旨在探讨MIC-1在早期非小细胞肺癌（non-small cell lung cancer, NSCLC）诊断及其与临床病理特征间的关系，以及与术后复发/转移及预后的相关性。方法 采用酶联免疫吸附试验（enzymelinked immunosorbent assay, ELISA）方法检测152例早期肺癌、48例肺良性疾病患者及105例正常对照人群血清MIC-1浓度，分析MIC-1诊断肺癌中的作用，同时分析血清MIC-1浓度与临床病理特征、复发/转移及预后的相关性。结果 早期肺癌患者组MIC-1血清水平高于正常对照组（P<0.001）和肺良性疾病组（P<0.001），设1,000 pg/mL为诊断肺癌的临界值，MIC-1检测肺癌的敏感性和特异性分别为70.4%和99.0% ［曲线下面积（area under curve, AUC）: 0.90；95%CI: 0.87-0.94］；MIC-1血清水平与年龄（P=0.001）、性别（P=0.03）有关，病理TNM分期T2的患者MIC-1血清水平高于T1患者（P=0.022）；血清MIC-1>1,465 pg/mL组的患者3年生存率为77.6%，低于血清MIC-1<1,465 pg/mL组的患者94.8%（P=0.022），Cox回归多因素分析结果显示，血清MIC-1>1,465 pg/mL是I期、II期NSCLC独立的预后因素（HR=3.37, 95%CI: 1.09-10.42, P=0.035）。结论 MIC-1作为血清肿瘤生物标志物，可能有助于提高肺癌早期诊断。MIC-1的检测对判断I期、II期NSCLC患者预后有预测价值，可能为其独立的预后指标。.