Systematic Identification And Dissection Of Important Super Enhancers In Breast Cancer

Abnormal gene expression driven by super enhancers plays a key role in the occurrence and development of tumors.However,how to systematically identify the super enhancers that play an important role in tumors,especially to explore the mechanism of their functional hierarchy during tumorigenesis,remains to be further studied.At the same time,as the second largest cancer in women around the world,breast cancer has a high degree of clinical heterogeneity,which cause distinct therapeutic effects of breast cancer treatment for different patients.Therefore,finding new clinical drugs and exploring new treatments have always been a hot issue in the field of breast cancer.Based on the above two points,we carried out the exploration of super enhancers in breast cancer.In our studIn our study,chromatin accessibility data and H3K27 ac histone modification data from breast cancer patients were collected,and 1,201 super enhancers were defined by bioinformatics methods.Multi-omics data including genomic data,transcriptome data,epigenomic data and clinical data were collected to systematically annotate super enhancers and enhancers.Previous studies have found that important super enhancers have specific epigenetic characteristics.Based on this priori knowledge,we proposed a comprehensive index C-score to screen out 300 super enhancers with potentially important functions in the occurrence and development of breast cancer.The importance of super enhancers was verified by gene function and breast cancer related SNPs enrichment.In order to further explore the functional hierarchy of super enhancers,5,782 hub enhancers that enrich breast cancer specific SNPs,breast cancer important FOXA1 binding sites and stronger gene expression regulation were screened by comprehensive index D-score.To explore the specific function of super enhancers in breast cancer,88 metastasic super enhancers were identified by differential analysis,and related bioinformatic verifications were performed.Our study not only propoOur study not only proposes a set of complete pipeline for identifying important super enhancers in cancer,but also systematically dissects the functional hierarchy of super enhancers.It is helpful to the screening of cancer therapeutic drug targets with super enhancers as the core,also has scientific and social significance.