IGF-1、IGFBP-4和PAPPA在非小细胞肺癌患者血清的浓度及其临床意义

Serum levels and clinical signifi cance of IGF1, IGFBP-4 and PAPPA in non-small cell lung cancer

背景与目的：胰岛素样生长因子1（insulin-like growth factor 1,IGF-1）和胰岛素生长因子结合蛋白4（insulin-like growth factor binding protein 4,IGFBP-4）能影响肿瘤细胞的增殖、分化和凋亡。妊娠相关血清蛋白A（pregnancy-associated plasma protein-A,PAPPA）在IGFBP-4依赖IGF-1调节肿瘤细胞的生长机制中的作用日益受关注。本研究通过检测非小细胞肺癌（non-small cell lung cancer,NSCLC）患者血清中IGF-1、IGFBP-4和PAPPA的浓度,并分析其临床意义。方法：采用酶联免疫吸附双抗体夹心法（ELISA）检测82例NSCLC患者和40名健康体检者血清中IGF-1、IGFBP-4和PAPPA的浓度,3者血清浓度相关性运用Spearman相关分析,NSCLC危险程度与3者血清浓度之间关系运用计算优势比（OR）的非条件Logistic回归分析。结果：NSCLC患者血清中IGF-1、IGFBP-4和PAPPA的浓度显著高于正常人,差异有统计学意义（P〈0.05）;IGF-1与PAPPA浓度呈显著正相关（r=0.835,P=0.000）,而IGF1与IGFPB-4浓度呈显著负相关（r=-0.612,P=0.000）;血清中IGFBP-4与PAPPA的表达量也呈显著负相关（r=-0.673,P=0.000）。NSCLC危险程度随血清中IGF-1（OR=2.28,95%CI：1.25-4.36,P=0.008）和PAPPA（OR=1.64,95%CI：0.89-3.01,P=0.046）的表达水平升高而增加,而高表达IGFBP-4（OR=0.54,95%CI：0.30-1.01,P=0.047）可降低NSCLC危险程度。结论：检测NSCLC患者血清中的IGF-1、IGFBP-4和PAPPA的浓度对肺癌的辅助诊断和生物学行为预测有重要意义;深入研究IGFs的信号转导通路中各因子与NSCLC发生、发展的关系是有意义的研究方向。

Background and purpose： It is increasingly focused on that insulin-like growth factor 1（IGF-1） and insulin-like growth factor binding protein 4（IGFBP-4） effect cell proliferation, differentiation and apoptosis of tumor cells, and pregnancy-associated plasma protein-A（PAPPA） plays an important role in IGF-1-dependent IGFBP-4 protease mechanism that regulats tumor cells＇ growth. This study aimed to investigate the serum levels and clinical signifi cance of IGF-1, IGFBP-4, and PAPPA in patients with non-small cell lung cancer（NSCLC）. Methods： IGF-1, IGFBP-4, and PAPPA plasma levels were measured by enzyme-linked immunosorbent assay from 82 patients with NSCLC and 40 control subjects, then the correlations between variables were assessed by Spearman correlation analysis, and associations between the IGFs variables and lung cancer risk were calculated through the odds ratio（OR） and its 95% confi dence interval（CI） with the use of unconditional logistic regression analysis. Results： Serum levels of IGF-1, IGFBP-4 and PAPPA in NSCLC patients were signifi cantly higher than those in the control group（P〈0.05）.There was a signifi cant positive correlation between the serum IGF-1 levels and PAPPA levels（r=0.835,P=0.000）, and a negative correlation with IGFBP-4 levels（r=-0.612,P=0.000）. IGFBP-4 and PAPPA levels were negatively correlated（r=-0.673, P=0.000）. High plasma levels of IGF-1（OR=2.28, 95%CI： 1.25-4.36,P=0.008） and PAPPA（OR=1.64, 95%CI： 0.89-3.01,P=0.046）were associated with an increased risk of lung cancer, however high plasma levels of IGFBP-4（OR=0.54, 95%CI： 0.30-1.01,P=0.047）were associated with reduced risk of lung cancer. Conclusion： To detect IGF-1, IGFBP-4 and PAPPA in serum in NSCLC patients is meaningful for the clinical auxiliary diagnosis and biology behavior prediction of NSCLC. And further study of signal transduction pathways of IGFs with the occurrence and development of NSCLC is a meaningful research direction.