title: Plasma microRNAs are associated with acute exacerbation in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high short-term mortality with unknown causes. To predict this malignant condition in clinics is challenging. In this study, we aim to demonstrate whether there are miRNAs that differ between AE-IPF and stable IPF, which may be served as reliable biomarker for AE-IPF prediction.
  
  
  METHODS
  Human fibrotic-associated miRNAs arrays were designed to detect miRNAs expression in plasma of 3 AE-IPF patients, 3 Stable-IPF (S-IPF) patients and 3 normal controls (NC). Differentially expressed miRNAs between AE-IPF and S-IPF patients were selected for further analyses. The validation studies were carried out in plasma of 12 AE-IPF patients, 45 S-IPF patients and 51 healthy control subjects. Signaling pathways and cellular processes interacted with validated miRNAs were predicted by DIANA-miRPath.
  
  
  RESULTS
  According to the array analysis, 6 miRNAs showed differentiated expression between AE-IPF and S-IPF patients (P < 0.05). In the validation studies, let-7d-5p was decreased in S-IPF and further decreased in AE-IPF, when compared to NC (0.0003 ± 0.0002 vs 0.003 ± 0.002, P < 0.01 and 0.0007 ± 0.0005 vs 0.003 ± 0.002, P < 0.01). While miR-25-3p was obviously decreased in S-IPF (0.0002 ± 0.0001 vs 0.0003 ± 0.0003, P < 0.01) but significantly increased in AE-IP (0.0023 ± 0.002 vs 0.0003 ± 0.0003, P < 0.01). In receiver-operator characteristic (ROC) curve analysis, the areas under the curve (AUCs) of miR-25-3p and let-7d-5p were 0.83 and 0.75, respectively. The sensitivity at fixed specificity of 90% was improved from 50% to 66.7% when the two miRNAs were combined. The functional prediction of miRNAs suggested that the loss of anti-fibrotic capacity and the gain of uncontrolled cell growth may be required in AE-IPF pathogenesis.
  
  
  CONCLUSIONS
  In conclusion, miR-25-3p and let-7d-5p in plasma were differentially expressed between AE-IPF and S-IPF. A combination of these two miRNAs may be a potential biomarker for AE-IPF from IPF.
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Min
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Fan
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Hourong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China. daijinghongnew@sina.com.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Dai
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Rd., Nanjing, 210093, China. qian_gao@nju.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Acute exacerbation; Idiopathic pulmonary fibrosis; let-7d-5p; miR-25-3p