Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis

• Published in: International journal of molecular sciences Vol. 21; no. 22; p. 8812
• Main Authors: Di Mauro, Stefania, Scamporrino, Alessandra, Fruciano, Mary, Filippello, Agnese, Fagone, Evelina, Gili, Elisa, Scionti, Francesca, Purrazzo, Giacomo, Di Pino, Antonino, Scicali, Roberto, Di Martino, Maria Teresa, Malaguarnera, Roberta, Malatino, Lorenzo, Purrello, Francesco, Vancheri, Carlo, Piro, Salvatore
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.11.2020; MDPI
• Subjects: Aged; Aged, 80 and over; Biomarkers; Biomarkers - blood; Biopsy; Case-Control Studies; Cell adhesion & migration; Chronic Disease; Cohort Studies; Correlation analysis; Cytokines; Dyspnea; Epigenetics; Female; Gene expression; Humans; Hypotheses; Idiopathic Pulmonary Fibrosis - diagnosis; Liquid Biopsy; Lung diseases; Male; MicroRNAs; Pathogenesis; Patients; Pneumonia; Pulmonary fibrosis; RNA, Long Noncoding - blood; RNA, Messenger - blood; RNAs; liquid-biopsy; biomarkers; IPF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228812

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2–5 years after diagnosis. Therefore, IPF patient identification represents an important and challenging clinical issue. Current research is still searching for novel reliable non-invasive biomarkers. Therefore, we explored the potential use of long non-coding RNAs (lncRNAs) and mRNAs as biomarkers for IPF. Methods: We first performed a whole transcriptome analysis using microarray (n = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects (n = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. Results: 1059 differentially expressed transcripts were identified. We confirmed the downregulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) lncRNA, hsa_circ_0001924 circularRNA, utrophin (UTRN) and Y-box binding protein 3 (YBX3) mRNAs. The two analyzed non-coding RNAs correlated with Forced Vital Capacity (FVC)% and Diffusing Capacity of the Lung for carbon monoxide (DLCO)% functional data, while coding RNAs correlated with smock exposure. All analyzed transcripts showed excellent performance in IPF identification with Area Under the Curve values above 0.87; the most outstanding one was YBX3: AUROC 0.944, CI 95% = 0.895–0.992, sensitivity = 90%, specificity = 88.9%, p-value = 1.02 × 10−13. Conclusions: This study has identified specific transcript signatures in IPF suggesting that validated transcripts and microarray data could be useful for the potential future identification of RNA molecules as non-invasive biomarkers for IPF.