Remodeling characteristics and construction of a survival prediction model based on enhancers and regulome in intestinal type gastric cancer

To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer, analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.

H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers. Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications. Based on the distribution characteristics of H3K27ac, the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored. The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.

The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues. Compared with normal gastric mucosa, the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer. A total of 8 847 enhancers with increased activity in intestinal type gastric cancer were identified, accounting for 8.3% of all enhancers, which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells. A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers, which was able to predict the overall survival of patients.

Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer. These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC, E2F3 and other genes. A prognosis model based on enhancer target genes is constructed.