In particular, we identified some key genes that play crucial roles in the malignant transformation of oral leukoplakia to oral cancer, including 4 hub genes (STAT5B, EGFR, PDGFRB, STAT5A), 5 intra-MAOC genes (RAF1, PDGFRB, SRC, PRKACA, EGFR), 5 inter-MAOC genes (PRKCA, MAPK1, MAPK3, ESR1, FYN) and 8 miRNAs (hsa-miR-499-5p, hsa-miR-549, hsa-miR-205, hsa-miR-525-5p, hsa-miR-21, hsa-miR-323-3p, hsa-miR-423-3p, hsa-miR-491-3p). This evidence concerns the gene ESR1 and Oral leukoplakia.