Proteomic analysis of plasma exosomes to differentiate malignant from benign pulmonary nodules

Kuang, Muyu; Tao, Xiaoting; Peng, Yizhou; Zhang, Wenjing; Pan, Yafang; Cheng, Lei; Yuan, Chongze; Zhao, Yue; Mao, Hengyu; Zhuge, Lingdun; Zhou, Zhenhua; Chen, Haiquan; Sun, Yihua

doi:10.1186/s12014-019-9225-5

Cited by 18 publications

(18 citation statements)

References 40 publications

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“…From GO analysis, DEGs in milk EVs from BLV-infected cattle were revealed to be meaningfully involved in major molecular functions, biological processes, and cellular components, and were categorized in distinct protein classes including cellular processes, metabolic processes, response to stimuli, cells, catalytic activity, binding, extracellular regions, and so on. These findings were consistent with those from previous studies, which had revealed EVs from many tumors/cancers to be engaged in various biological functions, such as immune modulatory features, protein binding, signal transduction, and so on [46][47][48]. The previous study reported that during BLV infection, gene involved in diverse biological procedure including cellular proliferation, innate immune response, and metabolic process [49].…”

Section: Discussionsupporting

confidence: 91%

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Ishikawa

Rahman

Yamauchi

et al. 2020

Viruses

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Milk extracellular vesicles (EVs) form an excellent source of mRNAs, microRNAs (miRNAs), proteins, and lipids that represent the physiological and pathological status of the host. Recent studies have reported milk EVs as novel biomarkers for many infectious diseases in both humans and animals. For example, miRNAs in milk EVs from cattle were used for early detection of bacterial infection in the mammary gland. Based on these findings, we hypothesized that mRNAs in milk EVs are suitable for gaining a better understanding of the pathogenesis of bovine leukemia virus (BLV) infection and prognosis of the clinical stage in cattle. For that purpose, milk EVs were isolated from BLV-infected and uninfected cattle, and mRNAs were investigated using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed mainly focusing on the differentially expressed genes (DEGs) in milk EVs from BLV-infected cattle. GO and KEGG analyses suggested the DEGs in milk EVs from BLV-infected cattle had involved in diverse molecular functions, biological processes, and distinct disease-related pathways. The present study suggested that BLV infection causes profound effects on host cellular activity, changing the mRNA expression profile in milk EVs obtained from BLV-infected cattle. Overall, our results suggested that the mRNA profile in milk EVs to be a key factor for monitoring the clinical stage of BLV infection. This is the first report of mRNA profiling of milk EVs obtained from BLV-infected cattle.

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Section: Discussionsupporting

confidence: 91%

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Ishikawa

Rahman

Yamauchi

et al. 2020

Viruses

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“…FGB is cleaved by thrombin to yield monomers that polymerize into insoluble fibrin, usually associated with coagulation disorders. Both exosomal FBG and FGG were found to be significantly increased in patients with malignant pulmonary nodules and evidence reveals its increasing interest of candidate diagnostic biomarkers for bladder and prostate cancer, among others [ 113 ]. ITIH4 is a protein involved in inflammatory responses and host–virus interaction processes.…”

Section: Discussionmentioning

confidence: 99%

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

et al. 2021

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Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs.

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“…All the differentially abundant proteins found by our DIGE-based approach are major, abundant constituents of plasma. Among them, plasma exosomal FGG was recently found with fibrinogen β chain as a protein marker discriminating benign from malignant pulmonary nodules [ 48 ], being a promising prognostic biomarker for ovarian cancer [ 50 ] or cardiovascular disease [ 81 ].…”

Section: Discussionmentioning

confidence: 99%

“…MS-based proteomic analysis has recently been applied to cancer cell-derived EVs, revealing important biogenesis pathways and improving our understanding of carcinogenesis and tumor progression [ 15 , 46 , 47 ]. Proteomic analyses of plasma-derived exosomes have already identified potential tumor biomarkers for diagnosis (e.g., malignant pulmonary nodules [ 48 ], breast [ 49 ]) or prognosis (ovarian [ 50 ]). Thus far, a proteomic analysis of plasma-derived EVs from HL patients has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence

et al. 2021

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Exosomes and other small extracellular vesicles (EVs) are potential sources of cancer biomarkers. Plasma-derived EVs have not yet been studied in pediatric Hodgkin lymphoma (HL), for which predictive biomarkers of relapse are greatly needed. In this two-part proteomic study, we used two-dimensional difference gel electrophoresis (2D-DIGE) followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) to analyze EV proteins of plasma collected at diagnosis from children with nodular sclerosis HL, relapsed or not. EVs isolated using membrane affinity had radii ranging from 20 to 130 nm and contained the programmed cell death 6-interacting (ALIX) and the tumor susceptibility gene 101 (TSG101) proteins, whereas calnexin (CANX) was not detected. 2D-DIGE identified 16 spots as differentially abundant between non-relapsed and relapsed HL (|fold change| ≥ 1.5, p < 0.05). LC–MS/MS identified these spots as 11 unique proteins, including five more abundant in non-relapsed HL (e.g., complement C4b, C4B; fibrinogen γ chain, FGG) and six more abundant in relapsed HL (e.g., transthyretin, TTR). Shotgun LC–MS/MS on pooled EV proteins from non-relapsed HL identified 161 proteins, including 127 already identified in human exosomes (ExoCarta data). This EV cargo included 89 proteins not yet identified in exosomes from healthy plasma. Functional interrogation by the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that the EV proteins participate in platelet degranulation and serine-type endopeptidase activity as the most significant Gene Ontology (GO) biological process and molecular function (p < 0.01).

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Proteomic analysis of plasma exosomes to differentiate malignant from benign pulmonary nodules

Cited by 18 publications

References 40 publications

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence

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