血清外体内fibulin-1检测在胃癌诊断中的应用

Detection and diagnostic application of serum exosomal fibulin-1 in the patients with gastric cancer

目的评价血清外体（exosome）内fibulin-1蛋白分子在胃癌诊断中的临床应用价值。方法 Exosome沉淀法提取胃癌细胞及胃上皮细胞上清、胃癌患者及体检健康人血清exosome;western blot、ELISA法检测exosome内fibulin-1蛋白的表达水平,绘制ROC曲线并进行诊断效能分析。结果胃癌细胞及其上清exosome内fibulin-1表达水平显著低于胃上皮细胞及其上清exosome;胃癌患者血清exosome内fibulin-1的表达水平（31.94±16.92）μg/mL明显低于体检健康者（47.16±17.27）μg/mL（P=0.045）;胃癌患者血清exosome内fibulin-1的ROC曲线下面积（AUC^ROC）是0.727 5,95%可信区间（CI）为0.569 4～0.885 6,cut off值为43.19μg/mL,敏感性为70%,特异性为75%。结论血清exosome内fibulin-1分子有望作为胃癌诊断的潜在新型分子标志物。

Objective To evaluate the clinical application value of serum exosomal fibulin-1 in the diagnosis of gastric cancer. Methods The exosomes from the supernatant of the cultured gastric cancer cells and gastric epithelial cells and the serum of the patients with gastric cancer and the healthy controls were isolated by Exo Quick-TCTM Tissue Culture Media Exosome Precipitation Solution and Exo Quick TM Exosome Precipitation Solution,respectively. The expression levels of fibulin-1 in gastric cancer cells and gastric epithelial cells and in exosomes were detected by western blot and ELISA,and its diagnostic efficacy was analyzed by the area under the receiver operating characteristic（ ROC） curve（ AUC）. Results The expression levels of fibulin-1 in gastric cancer cells and their supernatant were significantly lower than those in gastric epithelial cells and their supernatant. The expression level of fibulin-1 in the serum of the patients with gastric cancer（ [31. 94 ± 16. 92] μg / mL） was significantly lower than that in healthy controls（ [47. 16 ±17. 27] μg / mL,P = 0. 045）. The AUC^ROC,95% confidence interval,cut off value,sensitivity and specificity of exosomal fibulin-1 in serum of gastric cancer patients were 0. 727 5,0. 569 4-0. 885 6,43. 19 μg / mL,70% and 75%,respectively. Conclusion The detection of serum exosomal fibulin-1,a novel molecular marker,may be helpful for the diagnosis of gastric cancer.