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Open AccessArticle

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

1
Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy
2
Department of Clinical and Experimental Medicine, Respiratory Medicine Unit, A.O.U. “Policlinico-Vittorio Emanuele”, University of Catania, 95123 Catania, Italy
3
Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
4
School of Human and Social Sciences, “Kore” University of Enna, 94100 Enna, Italy
5
Department of Clinical and Experimental Medicine, Unit of Internal Medicine, Azienda Ospedaliera Cannizzaro, University of Catania, 95100 Catania, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(22), 8812; https://doi.org/10.3390/ijms21228812
Received: 28 October 2020 / Revised: 16 November 2020 / Accepted: 19 November 2020 / Published: 20 November 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: RNAs; biomarkers; IPF; liquid-biopsy RNAs; biomarkers; IPF; liquid-biopsy
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Di Mauro, S.; Scamporrino, A.; Fruciano, M.; Filippello, A.; Fagone, E.; Gili, E.; Scionti, F.; Purrazzo, G.; Di Pino, A.; Scicali, R.; Di Martino, M.T.; Malaguarnera, R.; Malatino, L.; Purrello, F.; Vancheri, C.; Piro, S. Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis. Int. J. Mol. Sci. 2020, 21, 8812.

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