Fig. 1

Study design. EV mRNA, CTC mRNA, CTC gDNA, and cfDNA were isolated from only 18ml of blood and mRNA profiling or variant profiling resulted in comparable data sets for comprehensive integration. Integrative statistical analyses performed included the analysis of the individual analytes and their prognostic value, while the combination of the analytes was analyzed from the section “Hierarchical clustering and the ELIMA.score” onwards. While hierarchical clustering was performed with prior knowledge about OS correlations, k-means clustering was performed without prior correlation information. A prerequisite for k-means clustering was determining the optimal number of stable clusters that could be formed, which was found by the elbow method. Mutual information and SVD analyses were carried out to determine whether or not it was necessary to use all the LBAs. With the results of the k-means clustering, we performed a graph-theoretic analysis to identify the salient parameters within the clusters