An integrated omics study on the role of HDAC9 gene in the oncogenic events of human gastrointestinal-tract associated cancers

Abstract

Esophageal, pancreatic, and colorectal cancers are considered as the main cancers associated with the gastrointestinal-tract taking a huge toll on human health. Exploring new cancer-critical genes for early diagnosis and treatment is of utmost importance for adopting an appropriate therapeutic strategy. Histone deacetylase 9 (HDAC9) is a class II histone-deacetylase that removes acetyl groups from lysine residues on the N-terminus of histones to repress transcription and mediates critical cellular processes including regulation of transcription and cell cycle. Herein, we present a comprehensive omics-based exploration of the oncogenomic relevance of HDAC9 in the neoplastic transformation events of human GI tract-associated cancers. Differential expression and oncogenomics of HDAC9 in various cancer forms, effect of HDAC9 mutation on survivability, association of different signaling pathways, immune infiltration, and protein-protein interaction have been deciphered through bioinformatics approaches. This bioinformatics study collectively revealed that abundance of HDAC9 mRNA is higher in esophageal and pancreatic cancer while lower in colorectal cancer. Moreover, transcriptional expression of HDAC9 was found to be negatively correlated with the survival of patients with pancreatic and colorectal cancer. Most of the subjects included in the study with perturbation of HDAC9 gene expression were noted to possess overactivation of vital signaling pathways, including TGF-β, RTK-RAS, Wnt, and p53 signaling pathways associated with oncogenesis. Taken together, this study proposes HDAC9 as a potential cancer-critical gene that could be considered a biomarker for the diagnosis and therapeutic intervention of human GI tract cancer.