An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer - read online free

Sep 24, 2026

Lung cancer remains a leading cause of cancer-related death, with non-small cell lung cancer showing poor 5-year survival and frequent relapse even after curative-intent therapy. 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. The study proposes a novel sEV protein biomarker signature to identify patients at risk of metastatic disease, enabling more personalized treatment decisions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Background

EMT and prognostic need in NSCLC

Small extracellular vesicles as liquid biomarkers

Study approach

sEV protein changes induced by EMT

Development of an sEV prognostic signature

ARTICLE [https://doi.org/10.1038/s42003-022-04350-4](https://doi.org/10.1038/s42003-022-04350-4) OPEN An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer Richard 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 ✉ Despite 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. 1 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. 7 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. ✉ email: [andreas.moller@qimrberghofer.edu.au](andreas.moller@qimrberghofer.edu.au) COMMUNICATIONS 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 Lung cancer is the most common cause of cancer-related mortality worldwide and has one of the lowest survival outcomes 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,

FAQs

Why are additional prognostic tools needed for NSCLC beyond TNM staging?

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.

What role does EMT play in NSCLC progression?

EMT involves epithelial cells shifting to elongated, mesenchymal phenotypes, supporting metastatic behavior and contributing to treatment-refractory disease and resistance to apoptotic stimuli.

How do small extracellular vesicles support the proposed prognostic strategy?

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.

Sep 24, 2026

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