Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) patients, which represent about 85% of all lung cancer cases, have a poor overall five-year survival rate, as low as 15%. Biopsies are used to diagnose and subtype NSCLC, and pathology-based TNM staging predicts survival and guides clinical interventions. However, TNM staging does not predict therapy responses for the individual patient. Additionally, biopsy-based diagnostic approaches are invasive, prone to sampling limitation, and are generally not repeated after the initial diagnosis.
Accurate prognostic biomarkers, in particular non-invasive liquid biomarkers, will allow clinicians to triage patients who require intensification of treatment or adjuvant treatment interventions. To date, there is no prognostic test capable of accurately predicting NSCLC patient outcomes.
We have developed a blood-based multi-protein signature capable of accurately prognosticating clinical outcome in two independent NSCLC patient cohorts. This signature is contained in small circulating nano-vesicles termed exosomes. The protein change is caused by hypoxia-induced epithelial-to-mesenchymal transition (EMT) happening within cancer cells. We furthermore show that EMT in cancer cells, mediated by exosomal transfer, can cause therapy resistance and metastasis.
Overall, this work describes a novel prognostic biomarker signature to identify early stage NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised adjuvant treatment decisions.