Fig. 4: Validation of EcoTyper risk scores (EcoRIS) on external melanoma datasets.
A Prognostic validation of EcoRIS in the E1609 dataset (n = 700): Kaplan-Meier overall survival curves compare patients categorized into low- (n = 350) and high-EcoRIS (n = 350) scores (based on the median). The forest plot describes five component ecotypes associated with HR. Analyses were conducted on the entire E1609 cohort (left) and Ipilimumab-treated sub-arm (n = 456) (right). B EcoRIS scores and its prognosis in the harmonized melanoma dataset (n = 334)20. Kaplan-Meier curves for overall survival over 50 months with log-rank p-values reported in individual datasets: Gide et al. (n = 72)17, Van Allen et al. (n = 39)19, and Liu et al. (n = 115)18. Stratification is based on within-cohort median scores. CE carcinoma ecotype, CR/PR complete response (CR)/partial response (PR), CTLA4 cytotoxic T-lymphocyte associated protein 4, H&E Hematoxylin, and eosin stain, IHC immunohistochemistry, OS overall survival, PD progressive disease, PD1 programmed cell death protein 1. C Representative slides of melanoma tissue stained with H&E and IHC for markers CD8 and CD20, shown from left to right. Images represent a patient with a low predicted risk score and another assigned to CE9. D Association of COMPASS-predicted TLS across ecotypes and concordance with COMPASS-predicted treatment response with EcoRIS. The left panel of Fig. 4D shows box plots of COMPASS-predicted TLS across ecotypes (p = 4.9 × 10−5, Wilcoxon test, n = 78(CE-CE8) vs. 35(CE9&10); p = 0.029, Wilcoxon test, n = 79 (Low CE9 group) vs. 80 (High CE9 group)). The box plot in the right panel of Fig. 4D displays demonstrates the concordance between COMPASS-predicted treatment response and EcoRIS (p = 5.8 × 10−8, Wilcoxon test, n = 55 responders vs. n = 104 non-responders). In all box plots, the central line marks the median, the lower and upper hinges denote the first and third quartiles, and the whiskers extend to 1.5 × the interquartile range (IQR).
