Plasma micro-RNA Levels are Associated with the Development of Chronic Lung Allograft Dysfunction after Bilateral Living-Donor and Cadaveric Lung Transplantation

T. Shiotani, S. Sugimoto, H. Yamamoto, D. Shimizu, K. Miyoshi, S. Otani, M. Okazaki, M. Yamane, T. Oto, S. Toyooka

Research output: Contribution to journalArticle

Abstract

PURPOSE: Micro-RNAs (miRNAs) regulate genes by selectively silencing their target messenger RNAs. Recently, serum levels of miRNA related to pulmonary fibrosis (miR-21 and miR-155), have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after cadaveric lung transplantation (CLT). We investigated the relationship between miRNAs levels and CLAD after bilateral living-donor lobar lung transplantation (LDLLT) and CLT. METHODS: Blood samples were collected from a total of 70 patients who underwent bilateral LDLLT (n=39) and bilateral CLT (n=31), including patients with CLAD (the CLAD group, n=25) and those without CLAD (the non-CLAD group, n=45). Plasma miRNA levels (miR-21 and miR-155) were quantified using real-time PCR and compared between the two groups. The relationship between miRNA levels and the results of pulmonary function tests at the onset of CLAD was assessed. Appropriate cut-off values of miRNA levels were set for the diagnosis of CLAD. RESULTS: The median follow-up period was 3074 (1071-7523) days. Plasma miRNA levels of the CLAD group were significantly higher than those of the non-CLAD group (miR-21, P<0.001; miR-155, P=0.013) (Fig. 1). In the CLAD group, miRNA levels after LDLLT were comparable to those after CLT. Moreover, miRNA levels were significantly negatively correlated with the baseline values of forced expiratory volume in 1 second (FEV1) (miR-21, P<0.001; miR-155, P=0.039) and those of total lung cavity (TLC) (miR-21, P<0.001; miR-155, P=0.0012) (Fig. 2). An ROC analysis of the performance of miR-21 level as a marker of CLAD yielded an AUC of 0.94 at a threshold level of 6.51. Patients with miR-21 level≥6.51 showed significantly better CLAD-free survival than those with miR-21 level<6.51 (P<0.001) (Fig. 3). CONCLUSION: Plasma miRNA levels are associated with the development of CLAD after bilateral LDLLT and CLT, and might be a potential biomarker for the diagnosis of CLAD.

Original languageEnglish
Pages (from-to)S194
JournalThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 1 2020

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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