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Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing

BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC....

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Autores principales: Zheng, Wei, Ye, Wangzhong, Wu, Zijie, Huang, Xinyi, Xu, Yuanji, Chen, Qinyan, Lin, Zhizhong, Chen, Yanyu, Bai, Penggang, Chen, Chuanben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011216/
https://www.ncbi.nlm.nih.gov/pubmed/33789676
http://dx.doi.org/10.1186/s12935-021-01881-4
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author Zheng, Wei
Ye, Wangzhong
Wu, Zijie
Huang, Xinyi
Xu, Yuanji
Chen, Qinyan
Lin, Zhizhong
Chen, Yanyu
Bai, Penggang
Chen, Chuanben
author_facet Zheng, Wei
Ye, Wangzhong
Wu, Zijie
Huang, Xinyi
Xu, Yuanji
Chen, Qinyan
Lin, Zhizhong
Chen, Yanyu
Bai, Penggang
Chen, Chuanben
author_sort Zheng, Wei
collection PubMed
description BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC. METHODS: Exosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples. RESULTS: Western blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes. CONCLUSIONS: We identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01881-4.
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spelling pubmed-80112162021-03-31 Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing Zheng, Wei Ye, Wangzhong Wu, Zijie Huang, Xinyi Xu, Yuanji Chen, Qinyan Lin, Zhizhong Chen, Yanyu Bai, Penggang Chen, Chuanben Cancer Cell Int Primary Research BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC. METHODS: Exosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples. RESULTS: Western blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes. CONCLUSIONS: We identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01881-4. BioMed Central 2021-03-31 /pmc/articles/PMC8011216/ /pubmed/33789676 http://dx.doi.org/10.1186/s12935-021-01881-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Primary Research
Zheng, Wei
Ye, Wangzhong
Wu, Zijie
Huang, Xinyi
Xu, Yuanji
Chen, Qinyan
Lin, Zhizhong
Chen, Yanyu
Bai, Penggang
Chen, Chuanben
Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title_full Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title_fullStr Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title_full_unstemmed Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title_short Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing
title_sort identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on rna sequencing
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011216/
https://www.ncbi.nlm.nih.gov/pubmed/33789676
http://dx.doi.org/10.1186/s12935-021-01881-4
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