2015 年第 3 期 第 13 卷

巨噬细胞抑制因子-1(MIC-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

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关键词：肺癌巨噬细胞抑制因子-1联合检测早期诊断

• 摘要：
• 【摘要】[目的] 研究巨噬细胞抑制因子-1（MIC-1）在较大样本的早期肺癌和肺癌中的辅助诊断价值，并评价多肿瘤标志物联合应用相关数据的临床意义。 [方法] 应用本实验室自主研制的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例不同临床分期的未治疗肺癌患者和488例健康人血清样本中的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，并研究多标志联合检测的价值。 [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水平随临床分期显著上升(p<0.001)，且与肿瘤浸润(p<0.001)、淋巴结转移(p=0.037)、远端转移(p<0.001)和肿瘤分化程度(p<0.001)显著相关。MIC-1肺癌诊断的敏感性高于其它五种肺癌标志物的联合应用(76.6% vs 72.2%)，在腺癌诊断中更为突出(腺癌：74.7% vs 68.9%；鳞癌：81.6% vs 82.8%；小细胞癌：84.9% vs 83.0%)。尤为显著的是，MIC-1诊断Ⅰ期和 Ⅱ期肺癌的敏感性可达70.2%和69.9%，显著优于五种常用标志物中敏感性最高的Cyfra21-1(Ⅰ期20.7%，Ⅱ期52.1%)；MIC-1联合上述五种标志物诊断Ⅰ期和Ⅱ期肺癌的灵敏度可达79.8%和87.7%。 [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联合检测用于健康人群体检和肺癌早期诊断具有重要的临床意义和价值。
• Objective: To investigate the accessory diagnostic value of macrophage inhibitory cytokine-1 (MIC-1) in large samples of 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. Methods: The levels and distribution of MIC-1, CEA, CA125, NSE, SCC and Cyfra21-1 in serum samples from 663 untreated patients with different clinical stages of lung cancer and 488 healthy 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 biomarkers was explored. Results: 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 metastasis (p=0.037), remote metastasis (p<0.001) and degrees of differentiation (p<0.001). The sensitivity of MIC-1 was even superior to the combination of the other five biomarkers (76.6% vs 72.2%), especially in the diagnosis of lung adenocarcinoma (adenocarcinoma: 74.7% vs 68.9%; squamous carcinoma: 81.6% vs 82.8%; small-cell lung cancer: 84.9% vs 83.0%). Notably, the sensitivities of MIC-1 were 70.2% and 69.9% in stage Ⅰand stage Ⅱ lung cancer respectively, significantly higher than those of Cyfra21-1(stage Ⅰ:20.7%, stage Ⅱ:52.1%) which represented the highest value of the five common biomarkers. Furthermore, the sensitivities of MIC-1 combined with the other five biomarkers in early-stage lung cancer were significantly increased to 79.8% in stageⅠand 87.7% in stage Ⅱ lung cancer. Conclusions: MIC-1 is a valuable biomarker of lung cancer, especially in detection of early-stage lung cancer. The results imply that the combination of MIC-1with CEA, CA125, NSE, SCC and Cyfra21-1 may have important clinical value in healthy physical examination and in the diagnosis of early-stage lung cancer.