巨噬细胞抑制因子-1及其联合多种标志物在肺癌早期诊断和诊断中的临床意义

目的：研究巨噬细胞抑制因子-1（macrophage inhibitory cytokine-1，MIC-1）在早期肺癌诊断中的辅助价值，并评价多种肿瘤标志物联合应用的临床意义。方法应用MIC-1定量检测试剂盒及Roche Cobas 601电化学发光免疫分析仪分别检测663例未经治疗的不同临床分期的肺癌患者和488例正常人群血清样本中的MIC-1、CEA、CA125、NSE、SCC和CYFRA21-1水平和分布，分析患者血清MIC-1水平与肺癌临床分期、病理分型和细胞分化程度的关系，并研究多种标志物联合检测的价值。结果肺癌患者血清MIC-1水平显著高于正常人群（P＜0.001）；MIC-1水平随临床分期的进展呈上升的趋势（P＜0.001），且与肿瘤浸润（P＜0.001）、淋巴结转移（P=0.02）、远端转移（P＜0.001）和肿瘤分化程度（P＜0.001）显著相关。单一检测MIC-1诊断肺癌的敏感度（76.6%）高于其他五种肺癌标志物的联合应用（72.2%），且MIC-1在鳞癌、腺癌、小细胞癌诊断中的敏感度均能达到甚至超过其他五种标志物的联合诊断水平（81.6%vs 82.8%；74.7%vs 68.9%；84.9%vs 83.0%）。在肺癌早期，以MIC-1为主的六种肿瘤标志物联合检测的诊断敏感度（Ⅰ期：79.8%；Ⅱ期：87.7%）显著高于其他五种肿瘤标志物联合诊断的敏感度（Ⅰ期：44.9%；Ⅱ期：72.6%）。结论 MIC-1是肺癌，尤其是早期肺癌有价值的血清肿瘤标志物，MIC-1和CEA、CA125、NSE、SCC、CYFRA21-1联合检测用于普通人群体检和肺癌早期诊断具有重要的临床意义和价值。

Clinical significance of macrophages inhibitory cytokine-1 and the combination with multiple biomarkers in the diagnosis and early diagnosis of lung cancer

Objective To investigate the accessory diagnostic value of macrophage inhibitory cytokine-1 (MIC-1) in patients with lung cancer, and estimate the clinical value of MIC-1 in combination with other biomarkers in the screening of early-stage lung cancer. Method The levels and distribution of MIC-1, CEA, CA125, NSE, SCC and Cyfra21-1 in serum samples from 663 previously untreated patients with different clinical stages of lung cancer and 488 healthy normal subjects were analyzed by self-produced MIC-1 double antibody sandwich ELISA Kit and Roche Cobas 601 ECL analyzer, respectively. The association of the serum levels of MIC-1 with clinical stages, pathologic types, and degrees of differentiation were analyzed. Additionally, the clinical value of MIC-1 and the combined bio-markers was explored. Result The serum levels of MIC-1 in patients with lung cancer were significantly higher than those in healthy control (P<0.001). A stepwise increase of MIC-1 levels was noted with the progress of lung cancer (P<0.001), and the levels were significantly correlated with the depth of tumor invasion (P<0.001), lymph node me-tastasis (P=0.02), remote metastasis (P<0.001) and degrees of differentiation (P<0.001). The sensitivity of MIC-1 was even superior to the parallel test of the other five biomarkers (76.6% vs 72.2%), specifically, displaying comparable or exceeding results in different pathological type of squamous carcinoma, adenocarcinoma and small-cell lung cancer (81.6% vs 82.8%; 74.7% vs 68.9%; 84.9% vs 83.0%). Furthermore, the sensitivities of MIC-1 combined with the oth-er five biomarkers in early-stage lung cancer were significantly increased from 44.9% to 79.8% in stage I and from 72.6% to 87.7% in stage II lung cancer. Conclusion MIC-1 is a valuable biomarker of lung cancer, especially in de-tection of early-stage lung cancer. The results imply that the parallel test of MIC-1 with CEA, CA125, NSE, SCC and Cyfra21-1 may have important clinical value in physical examination and in the diagnosis of early-stage lung can-cer.