Transcriptomic Profiling Identified Hub Genes Linking Barrett’s Esophagus and Esophageal Adenocarcinoma

Abstract

Abstract Background Barrett’s esophagus (BE) is a common type of metaplasia and is recognized as a precursor of esophageal adenocarcinoma (EAC). However, the gene expression pattern underlying the progression of BE and EAC remains to be comprehensively explained. Herein we performed transcriptomic analyses using public microarray data (158 EAC, 51 BE, and 27 control samples).Results Differentially expressed genes that were common and unique to BE and EAC were consequently identified. Further, NFE2L3 and MCM2 showed a higher effect size in EAC than in BE; we validated their biological functions in influencing cell proliferation using CRISPR screen data. We found that the common DEGs between EAC and BE were strongly enriched for development, differentiation, and proliferation in keratinocytes. Besides, our co-expression network revealed shared and distinct gene regulation patterns in EAC and BE. Cell markers of fibroblasts were enriched in EAC/BE-shared modules, suggesting the tissue microenvironment in BE undergoes similar dysregulation as in EAC. T cells were found to be enriched in EAC-specific modules, highlighting the involvement of the immune response against tumors. Moreover, we used an independent dataset from The Cancer Genome Atlas to validate hub genes in EAC-specific modules.Conclusions To summarize, our findings provide comprehensive insights into the gene expression profile of BE and EAC and highlight the potential roles of key regulator genes and hub genes, some of which may have a potential clinical application.