Identification and characterization of differentially co-expressed head-to-head gene pairs in pancreatic cancer

Head-to-head (H2H) gene pairs are an evolutionarily conserved genomic configuration (sharing a bidirectional promoter) with implications in cancer. This study investigates the transcriptional mechanisms of H2H genes in pancreatic ductal adenocarcinoma (PDAC). We found that H2H pairs involving housekeeping and tumor suppressor genes maintained a stabler expression correlation, while most pairs had reduced co-expression. Differential co-expression analysis revealed 15 H2H gene pairs significantly altered in PDAC. The gene pairs RPL7-RDH10 and STAC-RNF38 showed both high transcriptional factor similarity and differential co-expression, and enrichment analysis highlighted FOXC1 and YY1 as key regulators of altered H2H pairs. Our characterization of H2H transcriptional patterns in PDAC provides insights into bidirectional promoter disruption. The identified H2H gene signatures offer paired biomarker potential for improved PDAC detection. Further study of mechanisms maintaining H2H stability could spur new therapeutic approaches.