ESR1 and neoplasm: These hub targets were mainly related to tumorigenesis (STAT3, JUN, TP53, CDKN1A, FOS, and MYC), tumor immunity (IL6, RELA), and tumor mechanism (MAPK1, MAPK3, MAPK14, and ESR1) in CRC TME (Bettelli et al., 2005; Zhang et al., 2019; Sun et al., 2020; Stefani et al., 2021).