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Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria

BACKGROUND: In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the...

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Autores principales: Kaur, Hargobinder, Sehgal, Rakesh, Kumar, Archit, Sehgal, Alka, Bansal, Devendra, Sultan, Ali A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172720/
https://www.ncbi.nlm.nih.gov/pubmed/30286756
http://dx.doi.org/10.1186/s12967-018-1646-9
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author Kaur, Hargobinder
Sehgal, Rakesh
Kumar, Archit
Sehgal, Alka
Bansal, Devendra
Sultan, Ali A.
author_facet Kaur, Hargobinder
Sehgal, Rakesh
Kumar, Archit
Sehgal, Alka
Bansal, Devendra
Sultan, Ali A.
author_sort Kaur, Hargobinder
collection PubMed
description BACKGROUND: In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19–24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level. METHODS: We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein–protein and mRNA–miRNA networks to identify highly regulated miRNA. RESULTS: In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60–71% and 69–81% respectively and area under curve (AUC) of 0.7 (p < 0.05). Moreover, in silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA–miRNA networks, suggesting their putative role in complicated P. vivax malaria. CONCLUSION: miR-7977 might act as a potential biomarker for differentiating complicated P. vivax malaria from uncomplicated type. The elevated levels of miR-7977 may have a role to play in the disease pathology through UBA52 or TGF-beta signalling pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1646-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-61727202018-10-15 Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria Kaur, Hargobinder Sehgal, Rakesh Kumar, Archit Sehgal, Alka Bansal, Devendra Sultan, Ali A. J Transl Med Research BACKGROUND: In the recent years Plasmodium vivax has been reported to cause severe infections associated with mortality. Clinical evaluation has limited accuracy for the early identification of the patients progressing towards the fatal condition. Researchers have tried to identify the serum and the plasma-based indicators of the severe malaria. Discovery of MicroRNA (miRNA) has opened up an era of identification of early biomarkers for various infectious and non-infectious diseases. MicroRNAs (miRNA) are the small non-coding RNA molecules of length 19–24 nts and are responsible for the regulation of the majority of human gene expressions at post transcriptional level. METHODS: We identified the differentially expressed miRNAs by microarray and validated the selected miRNAs by qRT-PCR. We assessed the diagnostic potential of these up-regulated miRNAs for complicated P. vivax malaria. Futher, the bioinformtic analysis was performed to construct protein–protein and mRNA–miRNA networks to identify highly regulated miRNA. RESULTS: In the present study, utility of miRNA as potential biomarker of complicated P. vivax malaria was explored. A total of 276 miRNAs were found to be differentially expressed by miRNA microarray and out of which 5 miRNAs (hsa-miR-7977, hsa-miR-28-3p, hsa-miR-378-5p, hsa-miR-194-5p and hsa-miR-3667-5p) were found to be significantly up-regulated in complicated P. vivax malaria patients using qRT-PCR. The diagnostic potential of these 5 miRNAs were found to be significant with sensitivity and specificity of 60–71% and 69–81% respectively and area under curve (AUC) of 0.7 (p < 0.05). Moreover, in silico analysis of the common targets of up-regulated miRNAs revealed UBA52 and hsa-miR-7977 as majorly regulated hubs in the PPI and mRNA–miRNA networks, suggesting their putative role in complicated P. vivax malaria. CONCLUSION: miR-7977 might act as a potential biomarker for differentiating complicated P. vivax malaria from uncomplicated type. The elevated levels of miR-7977 may have a role to play in the disease pathology through UBA52 or TGF-beta signalling pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1646-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-04 /pmc/articles/PMC6172720/ /pubmed/30286756 http://dx.doi.org/10.1186/s12967-018-1646-9 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kaur, Hargobinder
Sehgal, Rakesh
Kumar, Archit
Sehgal, Alka
Bansal, Devendra
Sultan, Ali A.
Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title_full Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title_fullStr Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title_full_unstemmed Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title_short Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria
title_sort screening and identification of potential novel biomarker for diagnosis of complicated plasmodium vivax malaria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172720/
https://www.ncbi.nlm.nih.gov/pubmed/30286756
http://dx.doi.org/10.1186/s12967-018-1646-9
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