Stroma-derived extracellular vesicle mRNA signatures inform histological nature of prostate cancer


Posted: 2021-10-01 19:00:00
J Extracell Vesicles . 2021 Oct;10(12):e12150. doi: 10.1002/jev2.12150. Alex P Shephard 1 , Peter Giles 2 , Mariama Mbengue 1 , Amr Alraies 1 , Lisa K Spary 3 , Howard Kynaston 4 5 , Mark J Gurney 6 , Juan M Falcón-Pérez 7 8 9 , Félix Royo 7 8 , Zsuzsanna Tabi 1 , Dimitris Parthimos 1 , Rachel J Errington 1 , Aled Clayton 1 , Jason P Webber 1 10 Affiliations Expand Affiliations 1 Tissue Microenvironment Group, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK. 2 Wales Gene Park, Henry Welcome Building, Cardiff University, Cardiff, UK. 3 Wales Cancer Bank, University Hospital of Wales, Cardiff, UK. 4 Section of Surgery, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK. 5 Department of Urology, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff, UK. 6 Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. 7 Exosomes Lab. CICbioGUNE-BRTA, Parque Tecnologico, Derio, Spain. 8 Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain. 9 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. 10 Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, UK. Item in Clipboard Alex P Shephard et al. J Extracell Vesicles. 2021 Oct. Show details Display options Display options Format J Extracell Vesicles . 2021 Oct;10(12):e12150. doi: 10.1002/jev2.12150. Authors Alex P Shephard 1 , Peter Giles 2 , Mariama Mbengue 1 , Amr Alraies 1 , Lisa K Spary 3 , Howard Kynaston 4 5 , Mark J Gurney 6 , Juan M Falcón-Pérez 7 8 9 , Félix Royo 7 8 , Zsuzsanna Tabi 1 , Dimitris Parthimos 1 , Rachel J Errington 1 , Aled Clayton 1 , Jason P Webber 1 10 Affiliations 1 Tissue Microenvironment Group, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK. 2 Wales Gene Park, Henry Welcome Building, Cardiff University, Cardiff, UK. 3 Wales Cancer Bank, University Hospital of Wales, Cardiff, UK. 4 Section of Surgery, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK. 5 Department of Urology, Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff, UK. 6 Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. 7 Exosomes Lab. CICbioGUNE-BRTA, Parque Tecnologico, Derio, Spain. 8 Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain. 9 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. 10 Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, UK. Item in Clipboard CiteDisplay options Display options Format Abstract Histological assessment of prostate cancer is the key diagnostic test and can predict disease outcome. This is however an invasive procedure that carries associated risks, hence non-invasive assays to support the diagnostic pathway are much needed. A key feature of disease progression, and subsequent poor prognosis, is the presence of an altered stroma. Here we explored the utility of prostate stromal cell-derived vesicles as indicators of an altered tumour environment. We compared vesicles from six donor-matched pairs of adjacent-normal versus disease-associated primary stromal cultures. We identified 19 differentially expressed transcripts that discriminate disease from normal stromal extracellular vesicles (EVs). EVs isolated from patient serum were investigated for these putative disease-discriminating mRNA. A set of transcripts including Caveolin-1 (CAV1), TMP2, THBS1, and CTGF were found to be successful in discriminating clinically insignificant (Gleason = 6) disease from clinically significant (Gleason > 8) prostate cancer. Furthermore, correlation between transcript expression and progression-free survival suggests that levels of these mRNA may predict disease outcome. Informed by a machine learning approach, combining measures of the five most informative EV-associated mRNAs with PSA was shown to significantly improve assay sensitivity and specificity. An in-silico model was produced, showcasing the superiority of this multi-modal liquid biopsy compared to needle biopsy for predicting disease progression. This proof of concept highlights the utility of serum EV analytics as a companion diagnostic test with prognostic utility, which may obviate the need for biopsy. Keywords: RNA; biomarker; extracellular vesicles; prostate cancer; stroma. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. References REFERENCES Ahmed, H. U., El-Shater Bosaily, A., Brown, L. C., Gabe, R., Kaplan, R., Parmar, M. K., Collaco-Moraes, Y., Ward, K., Hindley, R. G., Freeman, A., Kirkham, A. P., Oldroyd, R., Parker, C., & Emberton, M. (2017). Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet (London, England), 389(10071), 815-822. Ayala, G., Tuxhorn, J. A., Wheeler, T. M., Frolov, A., Scardino, P. T., Ohori, M., Wheeler, M., Spitler, J., Rowley, D. R. (2003). Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clinical Cancer Research, 9(13), 4792-4801. Batra, J. S., Girdhani, S., & Hlatky, L. (2014). A quest to identify prostate cancer circulating biomarkers with a bench-to-bedside potential. Journal of Biomarkers, 2014, 321680. Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., Antipin, Y., Reva, B., Goldberg, A. P., Sander, C., & Schultz, N. (2012). The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discovery, 2(5), 401-404. Connell, S. P., Hanna, M., McCarthy, F., Hurst, R., Webb, M., Curley, H., Walker, H., Mills, R., Ball, R. Y., Sanda, M. G., Pellegrini, K. L., Patil, D., Perry, A. S., Schalken, J., Pandha, H., Whitaker, H., Dennis, N., Stuttle, C., Mills, I. G., & Clark, J. (2019). A four-group urine risk classifier for predicting outcome in prostate cancer patients. BJU International, 124(4), 609-620. Show all 50 references Grant support [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
2月 21, 2020 バイオアソシエイツ

エクソソームは脳卒中の顕著な回復を促進する

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