A blood-based miRNA signature with prognostic value for overall survival in advanced stage non-small cell lung cancer treated with immunotherapy.
Rajakumar T., Horos R., Jehn J., Schenz J., Muley T., Pelea O., Hofmann S., Kittner P., Kahraman M., Heuvelman M., Sikosek T., Feufel J., Skottke J., Nötzel D., Hinkfoth F., Tikk K., Daniel-Moreno A., Ceiler J., Mercaldo N., Uhle F., Uhle S., Weigand MA., Elshiaty M., Lusky F., Schindler H., Ferry Q., Sauka-Spengler T., Wu Q., Rabe KF., Reck M., Thomas M., Christopoulos P., Steinkraus BR.
Immunotherapies have recently gained traction as highly effective therapies in a subset of late-stage cancers. Unfortunately, only a minority of patients experience the remarkable benefits of immunotherapies, whilst others fail to respond or even come to harm through immune-related adverse events. For immunotherapies within the PD-1/PD-L1 inhibitor class, patient stratification is currently performed using tumor (tissue-based) PD-L1 expression. However, PD-L1 is an accurate predictor of response in only ~30% of cases. There is pressing need for more accurate biomarkers for immunotherapy response prediction. We sought to identify peripheral blood biomarkers, predictive of response to immunotherapies against lung cancer, based on whole blood microRNA profiling. Using three well-characterized cohorts consisting of a total of 334 stage IV NSCLC patients, we have defined a 5 microRNA risk score (miRisk) that is predictive of overall survival following immunotherapy in training and independent validation (HR 2.40, 95% CI 1.37-4.19; P