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This work examines epithelial-to-mesenchymal transition (EMT) and demonstrates that EMT-induced protein alterations in small extracellular vesicles can be detected in NSCLC patients and carry prognostic value. 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The study identifies EMT-induced protein signatures in sEVs that stratify risk.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},383220,1790748506,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962090883219,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","ARTICLE   \n [https://doi.org/10.1038/s42003-022-04350-4](https://doi.org/10.1038/s42003-022-04350-4)  OPEN  \nAn epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer  \nRichard J. Lobb1,2, Kekoolani S. Visan  1,2,11, Li-Ying Wu  1,3, Emma L. Norris4, Marcus L. Hastie4, Sarah Everitt5, Ian A. Yang6,7, Rayleen V. Bowman6,7, Shankar Siva5,8, Jill E. Larsen2,9, Jeffrey J. Gorman4, Michael MacManus5,8, Antoine Leimgruber10, Kwun M. Fong6,7 & Andreas Möller  1,2,3,11 ✉  \nDespite significant therapeutic advances, lung cancer remains the leading cause of cancerrelated death worldwide1. Non-small cell lung cancer (NSCLC) patients have a very poor overall five-year survival rate of only 10–20% . Currently, TNM staging is the gold standard for predicting overall survival and selecting optimal initial treatment options for NSCLC patients, including those with curable stages of disease. However, many patients with locoregionallyconfined NSCLC relapse and die despite curative-intent interventions, indicating a need for intensified, individualised therapies. Epithelial-to-mesenchymal transition (EMT), the phenotypic depolarisation of epithelial cells to elongated, mesenchymal cells, is associated with metastatic and treatment-refractive cancer. We demonstrate here that EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance. Overall, this work describes a novel prognostic biomarker signature that identifies potentially-curable NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised treatment decisions.  \n1 Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston QLD 4006, Australia. 2 Faculty of Medicine, University of Queensland, Brisbane QLD 4072, Australia. 3 School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane QLD 4001, Australia. 4 Protein Discovery Centre, QIMR Berghofer Medical Research Institute, Herston QLD 4006, Australia. 5 Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia. 6 UQ Thoracic Research Centre, The University of Queensland, Brisbane QLD 4072, Australia.  \n7 The Prince Charles Hospital, Brisbane QLD 4032, Australia. 8 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia. 9 Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Herston QLD 4006, Australia. 10 Swiss Medical Network, Genolier, VD 1272, Switzerland. 11 Present address: Department of Otorhinolaryngology, Chinese University of Hong Kong, Shatin, Hong Kong.  \n✉ email: [andreas.moller@qimrberghofer.edu.au](andreas.moller@qimrberghofer.edu.au)  \nCOMMUNICATIONS BIOLOGY | (2023)6:68 | [https://doi.org/10.1038/s42003-022-04350-4|www.nature.com/commsbio](https://doi.org/10.1038/s42003-022-04350-4|www.nature.com/commsbio) 1  \nLung cancer is the most common cause of cancer-related  \nmortality worldwide and has one of the lowest survival  \noutcomes of any cancer2. Most lung cancer cases are categorized as non-small cell lung cancer (NSCLC), and overall, NSCLC patients have an ~10–20% 5-year survival rate2. Tumour, node, metastasis (TNM) staging is currently the most important factor for predicting survival and guiding clinical interventions in NSCLC patients3. However, a significant proportion of potentially curable, locoregionally confined NSCLC patients have therapyrefractory disease or rapidly develop metastatic lesions despite curative-intent treatment4. This suggests that TNM staging alone is insufficient in guiding disease management. Therefore, there is a clinical demand to identify patients who respond poorly to current treatments, allowing for tailored treatment interventions. Experimental and clinical studies have verified hypoxia as adriver of cancer progression and metastasis5. Within the tumour microenvironment,","cbCainxJ3JIYJdtI","https://ap.wps.com/l/cbCainxJ3JIYJdtI","pdf",2268664,"English","# Background\n## EMT and prognostic need in NSCLC\n## Small extracellular vesicles as liquid biomarkers\n# Study approach\n## sEV protein changes induced by EMT\n## Development of an sEV prognostic signature","[{\"question\":\"Why are additional prognostic tools needed for NSCLC beyond TNM staging?\",\"answer\":\"Many locoregionally confined NSCLC patients relapse and die despite curative-intent treatment, showing that TNM staging alone is insufficient for guiding disease management and treatment intensity decisions.\"},{\"question\":\"What role does EMT play in NSCLC progression?\",\"answer\":\"EMT involves epithelial cells shifting to elongated, mesenchymal phenotypes, supporting metastatic behavior and contributing to treatment-refractory disease and resistance to apoptotic stimuli.\"},{\"question\":\"How do small extracellular vesicles support the proposed prognostic strategy?\",\"answer\":\"Small extracellular vesicles (sEVs) contain nucleic acids, lipids, and proteins derived from their cells of origin and can be released into circulation, making them accessible for non-invasive prognostic biomarker detection. The study identifies EMT-induced protein signatures in sEVs that stratify risk.\"}]","An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer - read online free | PDF",1790255287,23]