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

Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide. 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 locoregionally-confined 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.

Researchers at the QIMR Berghofer Medical Research Institute demonstrate 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.

Hypoxic sEV signature prognosticates disease progression in discovery NSCLC patient cohort

a, b SEVs isolated from NSCLC plasma display typical morphology as shown by TEM (a, size bar 200 nm), and size distribution of 30–150 nm (b). c TRPS demonstrates that there is no difference in sEV concentration in plasma from healthy controls, patients that progress within 18 months (early) or patients without progression at 36 months (late). d The hypoxic sEV signature proteins are upregulated in sEVs derived from patients that progress within 18 months. e ROC curve demonstrates that the hypoxic sEV signature is an excellent prognostic marker of disease progression (<18 months) in NSCLC patients with a sensitivity of 86% and specificity of 96%. f Kaplan–Meier curve shows a clear separation of patient DFS based on the abundance of proteins from the hypoxic sEV signature. ***p < 0.001.