Extended Data Fig. 8: Aneuploidy biomarker development in mNSCLC.
(a) PFS for COSINR patients with high aneuploidy score (AS, ≥median) (left) and low AS (<median, right) tumors; two-sided Log-rank test. (b) Scatter plot of AS and tumor purity (COSINR, n = 22 patients). (c) Comparison of number of pre-treatment organ sites by COSINR treatment arm and aneuploidy group (n = 22 patients); two-sided Wilcoxon test. Box plot elements are defined in the legend of Extended Data Figure 4b. (d) Association of clinical and pathological factors with overall survival in UC cohort (n = 58 patients). Variables tested were age, sex (M vs. F), presence of brain or liver metastases, smoking status (ever vs. never), PD-L1 expression (≥50% vs. <50%), histology (adenocarcinoma vs. other), number of disease sites, TMB, ECOG (0-1 vs. 2-3), and ICB paradigm (monotherapy vs. combination therapy). Variables significantly associated with OS are highlighted in blue; two-sided Wald test. (e) Distribution of AS in COSINR (n = 22 patients), UC (n = 58 patients), and TCGA (n = 500 patients) cohorts; dotted line represents high AS threshold (0.42). (f) Selection of optimal high AS threshold based on leave-one-out cross validation analysis; bars: 95% confidence interval; points: mean. Grey lines outline optimal AS threshold (0.42) (n = 58 patients). (g) Differences in OS in high AS (≥0.42) and low AS (<0.42) groups in UC validation cohort using the derived optimal threshold; two-sided Log-rank test. Dotted maroon and yellow lines represent subdivisions of the RT/ICB treatment group into patients treated with concurrent (maroon) or sequential (yellow) RT + ICB. (h) Application of the derived optimal threshold (0.42) to the COSINR cohort (OS); two-sided Log-rank test.
