The imbalance between acetylation and deacetylation of
histone proteins, important for epigenetic modifications, is closely associated with various diseases, including
cancer. However, knowledge regarding the modification of
histones across the different types of digestive
cancers is still lacking. The purpose of this research was to analyze the role of
histone acetylation and deacetylation in pan-digestive
cancers. We systematically characterized the molecular alterations and clinical relevance of 13
histone acetyltransferase (HAT) and 18
histone deacetylase (HDAC) genes in five types of digestive
cancers, including esophageal
carcinoma,
gastric cancer,
hepatocellular carcinoma,
pancreatic cancer, and
colorectal cancer. Recurrent mutations and copy number variation (CNV) were extensively found in acetylation-associated genes across pan-digestive
cancers. HDAC9 and KAT6A showed widespread copy number amplification across five pan-digestive
cancers, while ESCO2, EP300, and HDAC10 had prevalent copy number deletions. Accordingly, we found that HAT and HDAC genes correlated with multiple
cancer hallmark-related pathways, especially the
histone modification-related pathway, PRC2 complex pathway. Furthermore, the expression pattern of HAT and HDAC genes stratified patients with clinical benefit in
hepatocellular carcinoma and
pancreatic cancer. These results indicated that acetylation acts as a key molecular regulation of pan-digestive
tumor progression.