Use of the Malaria Protein VAR2CSA for the Detection of Small Extracellular Vesicles to Diagnose Adenocarcinoma
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| Název: | Use of the Malaria Protein VAR2CSA for the Detection of Small Extracellular Vesicles to Diagnose Adenocarcinoma |
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| Autoři: | Yaru Zhao, Chenlei Wen, Qi Wang, Yue Qing, Serena Tondi, Chiara Reina, Berina Šabanović, Cherry Yin‐Yi Chang, Chu‐Hu Lai, Huimin Wang, Mette Ø. Agerbaek, Thomas M. Clausen, Tobias Gustavsson, Thor G. Theander, Ali Salanti, Clara Csilla Meny, Baiyong Shen, Alexandra Aicher, Jiajia Tang, Christopher Heeschen |
| Zdroj: | J Extracell Vesicles Journal of Extracellular Vesicles, Vol 14, Iss 4, Pp n/a-n/a (2025) Zhao, Y, Wen, C, Wang, Q, Qing, Y, Tondi, S, Reina, C, Šabanović, B, Chang, C Y-Y, Lai, C-H, Wang, H, Agerbaek, M Ø, Clausen, T M, Gustavsson, T, Theander, T G, Salanti, A, Meny, C C, Shen, B, Aicher, A, Tang, J & Heeschen, C 2025, ' Use of the malaria protein VAR2CSA for the detection of small extracellular vesicles to diagnose adenocarcinoma ', Journal of Extracellular Vesicles, vol. 14, no. 4, e70067 . https://doi.org/10.1002/jev2.70067 |
| Informace o vydavateli: | Wiley, 2025. |
| Rok vydání: | 2025 |
| Témata: | Male, Short Communication, pancreatic ductal adenocarcinoma, Antigens, Protozoan, Proto-Oncogene Proteins p21(ras)/genetics, Proto-Oncogene Proteins p21(ras), Extracellular Vesicles, Antigens, Protozoan/metabolism, Cell Line, Tumor, Biomarkers, Tumor, Humans, Pancreatic Neoplasms/diagnosis, oncofetal chondroitin sulfate, Early Detection of Cancer, Aged, QH573-671, Chondroitin Sulfates, Extracellular Vesicles/metabolism, Middle Aged, Early diagnosis, recombinant malaria protein, Pancreatic Neoplasms, Biomarkers, Tumor/blood, Chondroitin Sulfates/metabolism, Female, Early Detection of Cancer/methods, extracellular vesicles, Cytology, Carcinoma, Pancreatic Ductal/diagnosis, Carcinoma, Pancreatic Ductal |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge for early diagnosis due to the lack of sensitive and specific biomarkers. This encouraged us to explore the diagnostic value of cancer‐derived small extracellular vesicles (sEVs) as early detection biomarkers. We previously showed that the recombinant malaria protein VAR2CSA (rVAR2) selectively binds to oncofetal chondroitin sulfate (ofCS) on the surfaces of cancer cells, which might be useful for identifying cancer‐derived sEVs. Indeed, flow cytometry revealed strong ofCS expression in PDAC cell‐derived sEVs, as evidenced by the presence of mutant KRAS, a common genetic alteration in PDAC. Plasma from PDAC patients showed significantly higher ofCS+ sEV levels compared to healthy donors and patients with benign gastrointestinal diseases. ROC analysis for ofCS+ sEVs revealed an AUC of 0.9049 for the detection of all‐stage and 0.9222 for early‐stage PDAC. Notably, mutant KRAS was also detected in these patient‐derived sEVs. Most intriguingly, combining ofCS+ sEVs and CA19‐9 resulted in an AUC of 0.9707 for the detection of early PDAC. Our study demonstrates that rVAR2 is suitable for detecting ofCS+ cancer‐derived sEVs in plasma, thereby providing high efficiency for identifying PDAC patients among a diverse population. These findings suggest that rVAR2‐based sEV detection could serve as a powerful diagnostic tool to improve patient survival through early detection. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2001-3078 |
| DOI: | 10.1002/jev2.70067 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/40241173 https://doaj.org/article/b4cd5088cd7047809e32e0abd7199185 https://curis.ku.dk/ws/files/449312105/Use_of_the_Malaria_Protein_VAR2CSA.pdf |
| Rights: | CC BY NC ND URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Přístupové číslo: | edsair.doi.dedup.....2f61157214ed9851f7b9332a2d494b56 |
| Databáze: | OpenAIRE |
| Abstrakt: | Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge for early diagnosis due to the lack of sensitive and specific biomarkers. This encouraged us to explore the diagnostic value of cancer‐derived small extracellular vesicles (sEVs) as early detection biomarkers. We previously showed that the recombinant malaria protein VAR2CSA (rVAR2) selectively binds to oncofetal chondroitin sulfate (ofCS) on the surfaces of cancer cells, which might be useful for identifying cancer‐derived sEVs. Indeed, flow cytometry revealed strong ofCS expression in PDAC cell‐derived sEVs, as evidenced by the presence of mutant KRAS, a common genetic alteration in PDAC. Plasma from PDAC patients showed significantly higher ofCS+ sEV levels compared to healthy donors and patients with benign gastrointestinal diseases. ROC analysis for ofCS+ sEVs revealed an AUC of 0.9049 for the detection of all‐stage and 0.9222 for early‐stage PDAC. Notably, mutant KRAS was also detected in these patient‐derived sEVs. Most intriguingly, combining ofCS+ sEVs and CA19‐9 resulted in an AUC of 0.9707 for the detection of early PDAC. Our study demonstrates that rVAR2 is suitable for detecting ofCS+ cancer‐derived sEVs in plasma, thereby providing high efficiency for identifying PDAC patients among a diverse population. These findings suggest that rVAR2‐based sEV detection could serve as a powerful diagnostic tool to improve patient survival through early detection. |
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| ISSN: | 20013078 |
| DOI: | 10.1002/jev2.70067 |
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