Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study

Non-Hodgkin lymphoma (NHL) is characterized by a great variability in patient outcomes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-associated ceRNA network for NHL....

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Main Authors: Mara Fernandes, Herlander Marques, Ana Luísa Teixeira, Rui Medeiros
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/6/1322
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author Mara Fernandes
Herlander Marques
Ana Luísa Teixeira
Rui Medeiros
author_facet Mara Fernandes
Herlander Marques
Ana Luísa Teixeira
Rui Medeiros
author_sort Mara Fernandes
collection DOAJ
description Non-Hodgkin lymphoma (NHL) is characterized by a great variability in patient outcomes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-associated ceRNA network for NHL. Using bioinformatic analysis, we identified the miRNA-lncRNA pairs, and using RT-qPCR, we analyzed their plasma levels in a cohort of 113 NHL patients to assess their prognostic value. Bioinformatic analysis identified SNHG16 and SNHG6 as hsa-miR-20a-5p and hsa-miR-181a-5p sponges, respectively. Plasma levels of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNG6 were significantly associated with more aggressive disease and IPI/FLIPI scores. Moreover, we found that patients with risk expression profiles of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 presented a higher risk of positive bone marrow involvement. Moreover, hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 pairs’ plasma levels were associated with overall survival and progression-free survival of NHL patients, being independent prognostic factors in a multivariate Cox analysis. The prediction models incorporating the ceRNA network expression analysis improved the predictive capacity compared to the model, which only considered the clinicopathological variables. There are still few studies on using the ceRNA network as a potential prognostic biomarker, particularly in NHL, which may permit the implementation of a more personalized management of these patients.
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spelling doaj.art-379d9998a822480cb498560c97fa08992023-11-23T15:42:47ZengMDPI AGBiomedicines2227-90592022-06-01106132210.3390/biomedicines10061322Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot StudyMara Fernandes0Herlander Marques1Ana Luísa Teixeira2Rui Medeiros3Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057 Braga, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalMolecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, PortugalNon-Hodgkin lymphoma (NHL) is characterized by a great variability in patient outcomes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-associated ceRNA network for NHL. Using bioinformatic analysis, we identified the miRNA-lncRNA pairs, and using RT-qPCR, we analyzed their plasma levels in a cohort of 113 NHL patients to assess their prognostic value. Bioinformatic analysis identified SNHG16 and SNHG6 as hsa-miR-20a-5p and hsa-miR-181a-5p sponges, respectively. Plasma levels of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNG6 were significantly associated with more aggressive disease and IPI/FLIPI scores. Moreover, we found that patients with risk expression profiles of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 presented a higher risk of positive bone marrow involvement. Moreover, hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 pairs’ plasma levels were associated with overall survival and progression-free survival of NHL patients, being independent prognostic factors in a multivariate Cox analysis. The prediction models incorporating the ceRNA network expression analysis improved the predictive capacity compared to the model, which only considered the clinicopathological variables. There are still few studies on using the ceRNA network as a potential prognostic biomarker, particularly in NHL, which may permit the implementation of a more personalized management of these patients.https://www.mdpi.com/2227-9059/10/6/1322non-Hodgkin lymphomamiRNAlncRNAceRNA networkprognosisbiomarker
spellingShingle Mara Fernandes
Herlander Marques
Ana Luísa Teixeira
Rui Medeiros
Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
Biomedicines
non-Hodgkin lymphoma
miRNA
lncRNA
ceRNA network
prognosis
biomarker
title Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
title_full Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
title_fullStr Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
title_full_unstemmed Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
title_short Circulating lncRNA- and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study
title_sort circulating lncrna and mirna associated cerna network as a potential prognostic biomarker for non hodgkin lymphoma a bioinformatics analysis and a pilot study
topic non-Hodgkin lymphoma
miRNA
lncRNA
ceRNA network
prognosis
biomarker
url https://www.mdpi.com/2227-9059/10/6/1322
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AT analuisateixeira circulatinglncrnaandmirnaassociatedcernanetworkasapotentialprognosticbiomarkerfornonhodgkinlymphomaabioinformaticsanalysisandapilotstudy
AT ruimedeiros circulatinglncrnaandmirnaassociatedcernanetworkasapotentialprognosticbiomarkerfornonhodgkinlymphomaabioinformaticsanalysisandapilotstudy