ESR1 and neoplasm: Although GSEA failed to detect any significant enrichment of the Ox-E/ER signature genes in ER-positive tumors according to clinical grade, Figure 4c demonstrates that a higher numeric Ox-E/ER signature index correlates significantly with higher tumor grade (rp = 0.20; P = 9.741 × e-05), with grade 3 tumors showing an approximately 1.2-fold higher Ox-E/ER index relative to lower grade tumors (t-test, P = 0.0002 against grade 1 and P = 0.001 against grade 2).