Fig. 5: Active regulatory super-enhancers predict candidate drugs against esophageal carcinogenesis and metastasis.

a, b Pie charts showing candidate drug compounds detected through the integrated analysis of common gained (a) and LNC-specific (b) super-enhancers with the Washington University Drug Gene Interaction Database. Three categories are highlighted in red. c TE1 cells were treated with eight chemical inhibitors separately or combinationally (AH + ML-030). Cells were counted at 72 h. Data were presented as mean values ± s.d. n = 3 biologically independent experiments examined. d Wound healing assays for control and shRNA expressing TE1 cells. The wound width was examined every 24 h, and the wound width at 0 h was normalized to “1”, and the relative width to the width at 0 h was calculated. Data were presented as mean values ± s.d. n = 3 biologically independent experiments examined. e–g Xenograft analysis of tumor growth. Immunodeficient nude mice injected with TE1 cells were treated with AH or ML-030, and tumor volumes were determined (e). The tumors were collected from sacrificed mice on day 21 for image acquisition (f) and tumor weight determination (g). For pooled data from five repeats, values indicate the mean ± s.d. A presentative data from n = 2 independent experiments was shown. e two-way ANOVA test with Geisser-Greenhouse correction, **P < 0.01. g unpaired t-test (two-tailed), **P < 0.01. h Expression of HSP90AA1 in Nor, EC, and LNC samples from our RNA-seq data. Data were presented as mean values ± s.d. n = 18 for Nor and EC; n = 14 for LNC. *P < 0.05, ****P < 0.0001, unpaired t-test (two-tailed). i The 2-year survival rate for two groups of patients (n = 9 for each group) possessing high or low HSP90AA1 expression as determined from clinical data in the present study. n = 3/9 (33.33%) in HSP90AA1-high and n = 6/9 (66.67%) HSP90AA1-low patients, presented as a single 2-year survival rate, were survival till Sep 2020. j The disease-free survival (DFS) rate was analyzed by comparing ESCC patient groups with high (n = 73) or low (n = 73) HSP90AA1 expression using GEPIA. Source data are provided as a Source Data file. A Log-rank test was performed for the survival data.