Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis
BackgroundPleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an es...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Surgery |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fsurg.2022.1050242/full |
| _version_ | 1797959961309872128 |
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| author | Xuede Zhang Lingling Bao Guohua Yu Haifeng Wang |
| author_facet | Xuede Zhang Lingling Bao Guohua Yu Haifeng Wang |
| author_sort | Xuede Zhang |
| collection | DOAJ |
| description | BackgroundPleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer.MethodsThe exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion.ResultsWe identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD via the exosomal hsa-miR-3120-5p-PRF1 axis.ConclusionsWe identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE. |
| first_indexed | 2024-04-11T00:39:06Z |
| format | Article |
| id | doaj.art-6036abee3a914f798085cfbcb4c9363f |
| institution | Directory Open Access Journal |
| issn | 2296-875X |
| language | English |
| last_indexed | 2024-04-11T00:39:06Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Surgery |
| spelling | doaj.art-6036abee3a914f798085cfbcb4c9363f2023-01-06T09:54:11ZengFrontiers Media S.A.Frontiers in Surgery2296-875X2023-01-01910.3389/fsurg.2022.10502421050242Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosisXuede Zhang0Lingling Bao1Guohua Yu2Haifeng Wang3Department of Oncology, Weifang People's Hospital, Weifang, ChinaDepartment of Hematology and Oncology, Beilun District People's Hospital, Ningbo, ChinaDepartment of Oncology, Weifang People's Hospital, Weifang, ChinaDepartment of Hematology and Oncology, Beilun District People's Hospital, Ningbo, ChinaBackgroundPleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer.MethodsThe exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion.ResultsWe identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD via the exosomal hsa-miR-3120-5p-PRF1 axis.ConclusionsWe identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE.https://www.frontiersin.org/articles/10.3389/fsurg.2022.1050242/fullexosomesmiRNAspleural effusionsbioinformatic analysislung adenocarcinoma |
| spellingShingle | Xuede Zhang Lingling Bao Guohua Yu Haifeng Wang Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis Frontiers in Surgery exosomes miRNAs pleural effusions bioinformatic analysis lung adenocarcinoma |
| title | Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| title_full | Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| title_fullStr | Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| title_full_unstemmed | Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| title_short | Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| title_sort | exosomal mirna profiling of pleural effusion in lung adenocarcinoma and tuberculosis |
| topic | exosomes miRNAs pleural effusions bioinformatic analysis lung adenocarcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fsurg.2022.1050242/full |
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