巨噬细胞抑制因子-1与早期非小细胞肺癌诊断及预后相关性

Macrophage Inhibitory Cytokine-1(MIC-1) as A Biomarker for Diagnosis and Prognosis of Stage Ⅰ-Ⅱ Non-small Cell Lung Cancer

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/m L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/m L组的患者3年生存率为77.6%,低于血清MIC-1<1,465 pg/m L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/m L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。

Background and objective Increased macrophage inhibitory cytokine-1 （MIC-1）, member of trans-forming growth factor-β（TGF-β） superfamily, was found in patients serum with epithelial tumors. hTerefore, 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 atfer 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 hTe level of MIC-1 of NSCLC patients was signiifcantly 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%speci-ifcity. hTe 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%speciifcity. hTe overall 3-year survival rate in patients with high level of MIC-1 （≥1,465 pg/mL） was signiifcantly 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 compro-mised overall survival （HR=3.37, 95%CI：1.09-10.42, P=0.035）. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.