Matrix metalloproteinase‑1 and microRNA‑486‑5p in urinary exosomes can be used to detect early lung cancer: A preliminary report

尿液外泌体中的基质金属蛋白酶-1和microRNA-486-5p可用于早期肺癌检测:初步报告

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作者:Wataru Ando ,Masaya Sogabe ,Shigemi Ishikawa ,Takayuki Uematsu ,Hiroyuki Furuya ,Hiroaki Yokomori ,Yutaka Kohgo ,Katsuya Otori ,Tomoyuki Nakano ,Shunsuke Endo ,Hiroyoshi Tsubochi ,Isao Okazaki

Abstract

The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890-1.974] vs. 0.600 (0.490-0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908-1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

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