SPP1 and neoplasm: Sig ESR1-H was enriched with metabolism-related genes, including CYP2A6 (FC = 3.83), CYP3A4 (FC = 3.78), CYP8B1 (FC = 3.38), and CYP1A2 (FC = 2.33) (Fig. 2a and Supplementary Fig. S2), whereas Sig ESR1-L exhibited enrichment with stemness-related or tumor aggressiveness-related genes, such as AFP (FC = −2.70), CD24 (FC = −2.27), S100P (FC = −2.01), SPP1 (FC = −1.89), EPCAM (FC = −1.