bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–03–26
seven papers selected by
Muhammad Rizwan, COMSATS University
  1. Applications of Exosome Vesicles in Different Cancer Types as Biomarkers.
  2. Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.
  3. ExosomePurity: tumour purity deconvolution in serum exosomes based on miRNA signatures.
  4. Improved exosome isolation methods from non-small lung cancer cells (NC1975) and their characterization using morphological and surface protein biomarker methods.
  5. Genetically Encoded FRET-Based Nanosensor for Real-Time Monitoring of A549 Exosomes: Early Diagnosis of Cancer.
  6. Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer.
  7. An exosome-related lncRNA signature correlates with prognosis, immune microenvironment, and therapeutic responses in hepatocellular carcinoma.
  1. Curr Mol Med. 2023 Mar 20.
    Applications of Exosome Vesicles in Different Cancer Types as Biomarkers.
    Murat Ihlamur, Kübra Kelleci, Yağmur Zengin.
      One of the biggest challenges in the fight against cancer is early detection. Early diagnosis is vital, but there are some barriers such as economic, cultural, and personal factors. Considering the disadvantages of radiological imaging techniques or serological analysis methods used in cancer diagnosis, such as being expensive, requiring expertise, and being time-consuming, there is a need to develop faster, more reliable, and cost-effective diagnostic methods for use in cancer diagnosis. Exosomes, which are responsible for intercellular communication with sizes ranging from 30-120 nm, are naturally produced biological nanoparticles. Thanks to the cargo contents they carry, they are a potential biomarker to be used in the diagnosis of cancer. Exosomes, defined as extracellular vesicles of endosomal origin, are effective in cancer growth, progression, metastasis, and drug resistance, and changes in microenvironmental conditions during tumor development change exosome secretion. Due to their high cellular activity, tumor cells produce much higher exosomes than healthy cells. Therefore, it is known that the number of exosomes in body fluids is significantly rich compared to other cells and can act as a stand-alone diagnostic biomarker. Cancer-derived exosomes have received great attention in recent years for the early detection of cancer and the evaluation of therapeutic response. In this article, the content, properties, and differences of exosomes detected in common types of cancer (lung, liver, pancreas, ovaries, breast, colorectal), which are the leading causes of cancer-related deaths, are reviewed. We also discuss the potential utility of exosome contents as a biomarker for early detection, which is known to be important in targeted cancer therapy.
    Keywords:  Exosome; biomarker; breast cancer; cancer; diagnosis; miRNA; vesicles
    DOI:  https://doi.org/10.2174/1566524023666230320120419
  2. Carcinogenesis. 2023 Mar 20. pii: bgad013. [Epub ahead of print]
    Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.
    Keshu Liu, Rongzhang Dou, Chaogang Yang, Ziyang Di, Dongdong Shi, Chunxiao Zhang, Jialin Song, Yan Fang, Sihao Huang, Zhenxian Xiang, Weisong Zhang, Shuyi Wang, Bin Xiong.
      Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC)tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.
    Keywords:  EMT; colorectal cancer; exosomes; metastasis; miR-29a
    DOI:  https://doi.org/10.1093/carcin/bgad013
  3. Brief Bioinform. 2023 Mar 24. pii: bbad119. [Epub ahead of print]
    ExosomePurity: tumour purity deconvolution in serum exosomes based on miRNA signatures.
    Tao Wu, Yao Dai, Yue Xu, Jie Zheng, Shuting Chen, Yinuo Zhang, Peng Tian, Xiaoqi Zheng, Haiyun Wang.
      Exosomes cargo tumour-characterized biomolecules secreted from cancer cells and play a pivotal role in tumorigenesis and cancer progression, thus providing their potential for non-invasive cancer monitoring. Since cancer cell-derived exosomes are often mixed with those from healthy cells in liquid biopsy of tumour patients, accurately measuring the purity of tumour cell-derived exosomes is not only critical for the early detection but also essential for unbiased identification of diagnosis biomarkers. Here, we propose 'ExosomePurity', a tumour purity deconvolution model to estimate tumour purity in serum exosomes of cancer patients based on microribonucleic acid (miRNA)-Seq data. We first identify the differently expressed miRNAs as signature to distinguish cancer cell- from healthy cell-derived exosomes. Then, the deconvolution model was developed to estimate the proportions of cancer exosomes and normal exosomes in serum. The purity predicted by the model shows high correlation with actual purity in simulated data and actual data. Moreover, the model is robust under the different levels of noise background. The tumour purity was also used to correct differential expressed gene analysis. ExosomePurity empowers the research community to study non-invasive early diagnosis and to track cancer progression in cancers more efficiently. It is implemented in R and is freely available from GitHub (https://github.com/WangHYLab/ExosomePurity).
    Keywords:  ExosomePurity; early diagnosis; miRNA-Seq; tumour exosomes; tumour purity
    DOI:  https://doi.org/10.1093/bib/bbad119
  4. J Cancer Res Clin Oncol. 2023 Mar 25.
    Improved exosome isolation methods from non-small lung cancer cells (NC1975) and their characterization using morphological and surface protein biomarker methods.
    Elham O Mahgoub, Galal M Abdella.
      This study has demonstrated improved methods for isolating exosomes from non-small lung cancer cells, which address the problems characterized by exosome morphological and chemical methods. To improve the isolation methods, cells from the NCI 1975 cell line were used as the source for exosomes. The isolation processes were carried out using serial isolation techniques in addition to specific preservation tools. The isolated exosomes were characterized using transmission electron microscopy (TEM), and scanning electron microscopy (SEM) was added for further assurance of the investigation results. The statistical analysis results showed that the size distributions of apoptotic vesicles (APV) 450 nm and necrotic bodies (NCB) 280 nm (extracellular vesicles) were significantly different from exosomes (P < 0.001). In contrast, the exosome size distribution was not significantly different from the published exosome sizes, as demonstrated by statistical analysis tools. This study confirmed the improved methods for isolating exosomes that make exosomes accessible for use in the diagnosis and prognosis of non-small cell lung cancer (NSCLC).
    Keywords:  Biomarker; Exosome; Extracellular vesicle (EVs); NCI1975; Non-small lung cancer cell
    DOI:  https://doi.org/10.1007/s00432-023-04682-6
  5. Anal Chem. 2023 Mar 23.
    Genetically Encoded FRET-Based Nanosensor for Real-Time Monitoring of A549 Exosomes: Early Diagnosis of Cancer.
    Reshma Bano, Neha Soleja, Mohd Mohsin.
      Exosomes contain a plethora of unique disease biomarkers involving cellular homeostasis, infection dissemination, cancer development, and cardiac diseases. Exosomes originating from cancer cells have promising biomarkers for the early detection and assessment of the therapeutic response to cancer. The exosomal epidermal growth factor receptor (EGFR) is a potential biomarker which is overexpressed in cancer; thus, the level of EGFR expression is investigated by so many methods in a liquid and solid biopsy. The optimal method for isolating pure exosomal EGFRs has not been well understood so far. Current approaches are complicated and time-consuming, therefore hampering their clinical applications. Here, we demonstrate the creation of an innovative fluorescence resonance energy transfer (FRET) sensor, named ExoSen (exosome sensor), which can be implemented to determine the concentration of exosomal EGFRs at in vitro as well as in vivo levels. In this study, a sensing element for A549 exosomes, mitogen-inducible gene 6 (MIG6), has been employed between the FRET pair ECFP and Venus. MIG6 binding to ExoSen induced a conformational change that can be monitored by a variation in the FRET ratio. Moreover, the developed sensor, expressed in bacterial, yeast, and HEK-293T cells, demonstrates an increased FRET ratio with the addition of A549 exosomes, which can quantify the A549 exosomes noninvasively. The ExoSen enables rapid detection of A549 exosomes with great sensitivity at a concentration of 3.5 × 109 particles/mL. ExoSen is stable to pH fluctuations and provides a highly accurate, real-time optical readout in cell-based experiments by using confocal microscopy.
    DOI:  https://doi.org/10.1021/acs.analchem.2c05774
  6. Transl Oncol. 2023 May;pii: S1936-5233(23)00038-4. [Epub ahead of print]31 101652
    Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer.
    Tiankang Li, Tingting Zhou, Jin Wu, Heng Lv, Hui Zhou, Mingnan Du, Xiuzhong Zhang, Nai Wu, Shuai Gong, Zeqiang Ren, Pengbo Zhang, Chong Zhang, Guangpu Liu, Xin Liu, Yi Zhang.
       BACKGROUND: Although circular RNAs (circRNAs) have recently garnered interest as disease markers, they have been relatively poorly studied as a biomarker in colorectal cancer (CRC). In this study, we aimed to screen the exosome-derived circRNAs in CRC and explore their potential as diagnostic and prognostic biomarkers of CRC METHODS: Exosomes were extracted from the plasma using a kit and validated by immunoblotting, transmission electron microscopy, and particle size analysis. The microarray datasets were employed to identify differentially-expressed circRNAs from plasma exosomes. Real-time quantitative reverse transcription PCR (RT-qPCR) verified the results of the microarray analysis, and Receiver operating characteristic (ROC) curve revealed the diagnostic ability of a single circRNA. The Starbase combined with microT, miRmap, and RNA22 were used to establish a circRNA-miRNA-mRNA network. Gene ontology, Kyoto Encyclopedia of Genes, Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were applied to determine potential functions of the identified mRNAs RESULTS: Comparing the microarray of plasma exosome-derived circRNAs and the microarray downloaded from the GEO database, 15 candidate circRNAs with up-regulated expression were identified. RT-qPCR verified that hsa_circ_0003270 (circGAPVD1) was upregulated in CRC plasma exosomes. ROC analysis showed that circGAPVD1 in plasma exosomes has potential diagnostic value for CRC. The sensitivity and specificity of circGAPVD1 in the diagnosis of CRC were found to be 75.64 and 71.79%, respectively (area under ROC = 0.7662). Furthermore, the lymph node metastasis and TNM staging of patients were positively correlated with high expression of circGAPVD1. Combined with the ENCORI database and GEO datasets, we identified the circGAPVD1-related ceRNA network. The enrichment analysis revealed that key nodes in the ceRNA network participate in many important signaling pathways such as protein post-translational modifications CONCLUSION: Our results revealed the diagnostic efficiency of circGAPVD1 in plasma exosomes. The highly expressed circGAPVD1 is expected to be a novel diagnostic marker for CRC.
    Keywords:  Biomarkers; Circular RNA; Colorectal cancer; Diagnosis; Exosomes; ceRNA network
    DOI:  https://doi.org/10.1016/j.tranon.2023.101652
  7. Transl Oncol. 2023 May;pii: S1936-5233(23)00037-2. [Epub ahead of print]31 101651
    An exosome-related lncRNA signature correlates with prognosis, immune microenvironment, and therapeutic responses in hepatocellular carcinoma.
    Wang Peng, Shuya Bai, Mengli Zheng, Wei Chen, Yanlin Li, Yilei Yang, Yuchong Zhao, Si Xiong, Ronghua Wang, Bin Cheng.
       BACKGROUND: Exosomes act as essential modulators of cancer development and progression in hepatocellular carcinoma. However, little is known about the potential prognostic value and underlying molecular features of exosome-related long non-coding RNAs.
    METHODS: Genes associated with exosome biogenesis, exosome secretion, and exosome biomarkers were collected. Exosome-related lncRNA modules were identified using PCA and WGCNA analysis. A prognostic model based on data from the TCGA, GEO, NODE, and ArrayExpress was developed and validated. A comprehensive analysis of the genomic landscape, functional annotation, immune profile, and therapeutic responses underlying the prognostic signature was performed on multi-omics data, and bioinformatics methods were also applied to predict potential drugs for patients with high risk scores. qRT-PCR was used to validate the differentially expressed lncRNAs in normal and cancer cell lines.
    RESULTS: Twenty-six hub lncRNAs were identified as highly correlated with exosomes and overall survival and were used for prognosis modeling. Three cohorts consistently showed higher scores in the high-risk group, with an AUC greater than 0.7 over time. These higher scores implied poorer overall survival, higher genomic instability, higher tumor purity, higher tumor stemness, pro-tumor pathway activation, lower anti-tumor immune cell and tertiary lymphoid structure infiltration, and poor responses to immune checkpoint blockade therapy and transarterial chemoembolization therapy.
    CONCLUSION: Through developing an exosome-related lncRNA predictor for HCC patients, we revealed the clinical relevance of exosome-related lncRNAs and their potential as prognostic biomarkers and therapeutic response predictors.
    Keywords:  Biomarker; Exosomes; Hepatocellular carcinoma; Long non-coding RNA; Therapeutic response; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.tranon.2023.101651
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