Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer
Abstract mRNA‐based molecular subtypes have implications for bladder cancer prognosis and clinical benefit from certain therapies. Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. We performed whole transcriptome RNA sequencing for formalin fixed...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12402 |
| _version_ | 1797296110879899648 |
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| author | Liang Dong Mingxiao Feng Morgan D. Kuczler Kengo Horie Chi‐Ju Kim Zehua Ma Kara Lombardo Heather Lyons Sarah R. Amend Max Kates Trinity J. Bivalacqua David McConkey Wei Xue Woonyoung Choi Kenneth J. Pienta |
| author_facet | Liang Dong Mingxiao Feng Morgan D. Kuczler Kengo Horie Chi‐Ju Kim Zehua Ma Kara Lombardo Heather Lyons Sarah R. Amend Max Kates Trinity J. Bivalacqua David McConkey Wei Xue Woonyoung Choi Kenneth J. Pienta |
| author_sort | Liang Dong |
| collection | DOAJ |
| description | Abstract mRNA‐based molecular subtypes have implications for bladder cancer prognosis and clinical benefit from certain therapies. Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. We performed whole transcriptome RNA sequencing for formalin fixed paraffin embedded (FFPE) tumour tissues and sEVs separated from matched tissue explants, urine and plasma in patients with bladder cancer. sEVs were separated using size‐exclusion chromatography, and characterized by transmission electron microscopy, nano flow cytometry and western blots, respectively. High yield of sEVs were obtained using approximately 1 g of tissue, incubated with media for 30 min. FFPE tumour tissue and tumour tissue‐derived sEVs demonstrated good concordance in molecular subtype classification. All urinary sEVs were classified as luminal subtype, while all plasma sEVs were classified as Ba/Sq subtype, regardless of the molecular subtypes indicated by their matched FFPE tumour tissue. The comparison within urine sEVs, which may exclude the sample type specific background, could pick up the different biology between NMIBC and MIBC, as well as the signature genes related to molecular subtypes. Four candidate sEV‐related bladder cancer‐specific mRNA biomarkers, FAM71E2, OR4K5, FAM138F and KRTAP26‐1, were identified by analysing matched urine sEVs, tumour tissue derived sEVs, and adjacent normal tissue derived sEVs. Compared to sEVs separated from biofluids, tissue‐derived sEVs may reflect more tissue‐ or disease‐specific biological features. Urine sEVs are promising biomarkers to be used for liquid biopsy‐based molecular subtype classification, but the current algorithm needs to be modified/adjusted. Future work is needed to validate the four new bladder cancer‐specific biomarkers in large cohorts. |
| first_indexed | 2024-03-07T21:58:38Z |
| format | Article |
| id | doaj.art-ece9db0272414a03a5178ffe2e145ee8 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-07T21:58:38Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-ece9db0272414a03a5178ffe2e145ee82024-02-24T09:50:27ZengWileyJournal of Extracellular Vesicles2001-30782024-02-01132n/an/a10.1002/jev2.12402Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancerLiang Dong0Mingxiao Feng1Morgan D. Kuczler2Kengo Horie3Chi‐Ju Kim4Zehua Ma5Kara Lombardo6Heather Lyons7Sarah R. Amend8Max Kates9Trinity J. Bivalacqua10David McConkey11Wei Xue12Woonyoung Choi13Kenneth J. Pienta14Department of Urology Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai ChinaThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Urology Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai ChinaThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Urology Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Urology Renji Hospital, Shanghai Jiao Tong University School of Medicine Shanghai ChinaThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland USAAbstract mRNA‐based molecular subtypes have implications for bladder cancer prognosis and clinical benefit from certain therapies. Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. We performed whole transcriptome RNA sequencing for formalin fixed paraffin embedded (FFPE) tumour tissues and sEVs separated from matched tissue explants, urine and plasma in patients with bladder cancer. sEVs were separated using size‐exclusion chromatography, and characterized by transmission electron microscopy, nano flow cytometry and western blots, respectively. High yield of sEVs were obtained using approximately 1 g of tissue, incubated with media for 30 min. FFPE tumour tissue and tumour tissue‐derived sEVs demonstrated good concordance in molecular subtype classification. All urinary sEVs were classified as luminal subtype, while all plasma sEVs were classified as Ba/Sq subtype, regardless of the molecular subtypes indicated by their matched FFPE tumour tissue. The comparison within urine sEVs, which may exclude the sample type specific background, could pick up the different biology between NMIBC and MIBC, as well as the signature genes related to molecular subtypes. Four candidate sEV‐related bladder cancer‐specific mRNA biomarkers, FAM71E2, OR4K5, FAM138F and KRTAP26‐1, were identified by analysing matched urine sEVs, tumour tissue derived sEVs, and adjacent normal tissue derived sEVs. Compared to sEVs separated from biofluids, tissue‐derived sEVs may reflect more tissue‐ or disease‐specific biological features. Urine sEVs are promising biomarkers to be used for liquid biopsy‐based molecular subtype classification, but the current algorithm needs to be modified/adjusted. Future work is needed to validate the four new bladder cancer‐specific biomarkers in large cohorts.https://doi.org/10.1002/jev2.12402bladder cancerextracellular vesiclesliquid biopsymolecular subtypetissue derived EV |
| spellingShingle | Liang Dong Mingxiao Feng Morgan D. Kuczler Kengo Horie Chi‐Ju Kim Zehua Ma Kara Lombardo Heather Lyons Sarah R. Amend Max Kates Trinity J. Bivalacqua David McConkey Wei Xue Woonyoung Choi Kenneth J. Pienta Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer Journal of Extracellular Vesicles bladder cancer extracellular vesicles liquid biopsy molecular subtype tissue derived EV |
| title | Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| title_full | Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| title_fullStr | Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| title_full_unstemmed | Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| title_short | Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| title_sort | tumour tissue derived small extracellular vesicles reflect molecular subtypes of bladder cancer |
| topic | bladder cancer extracellular vesicles liquid biopsy molecular subtype tissue derived EV |
| url | https://doi.org/10.1002/jev2.12402 |
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