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

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 bio...

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Published inInternational 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
LanguageEnglish
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
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms21228812

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Abstract 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.
AbstractList 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.
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. We first performed a whole transcriptome analysis using microarray ( = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects ( = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. 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%, -value = 1.02 × 10 . 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.
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.BACKGROUNDIdiopathic 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.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.METHODSWe 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.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.RESULTS1059 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.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.CONCLUSIONSThis 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.
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.
Author Purrello, Francesco
Di Mauro, Stefania
Malaguarnera, Roberta
Malatino, Lorenzo
Gili, Elisa
Vancheri, Carlo
Fagone, Evelina
Scamporrino, Alessandra
Purrazzo, Giacomo
Di Pino, Antonino
Fruciano, Mary
Filippello, Agnese
Piro, Salvatore
Scicali, Roberto
Di Martino, Maria Teresa
Scionti, Francesca
AuthorAffiliation 5 Department of Clinical and Experimental Medicine, Unit of Internal Medicine, Azienda Ospedaliera Cannizzaro, University of Catania, 95100 Catania, Italy; malatino@unict.it
3 Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy; fscionti20@gmail.com (F.S.); teresadm@unicz.it (M.T.D.M.)
2 Department of Clinical and Experimental Medicine, Respiratory Medicine Unit, A.O.U. “Policlinico-Vittorio Emanuele”, University of Catania, 95123 Catania, Italy; maryfruciano@yahoo.it (M.F.); efagone@unict.it (E.F.); elisagili@hotmail.com (E.G.)
1 Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95122 Catania, Italy; 8stefaniadimauro6@gmail.com (S.D.M.); alessandraska@hotmail.com (A.S.); agnese.filippello@gmail.com (A.F.); giacomopurr@hotmail.it (G.P.); antonino.dipino@unict.it (A.D.P.); robertoscicali@gmail.com (R.S.); fpurrell@unict.it (F.P.); salvatore.piro@unict.it (S.P.)
4 School of Hum
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Keywords RNAs
liquid-biopsy
biomarkers
IPF
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Snippet Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2–5 years after diagnosis. Therefore, IPF patient...
Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2-5 years after diagnosis. Therefore, IPF patient...
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StartPage 8812
SubjectTerms 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
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Title Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis
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