Influence of Epigenetic Regulators Expression on Gastric Cancer Prognosis

Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. High mortality is largely associated with late diagnosis and tumor heterogeneity, highlighting the need for molecular insights. Epigenetic alterations, including histone modifications and DNA/RNA methylation, play a key role in gene regulation, tumor progression, and therapy response. This study analyzed 179 samples (156 tumor, 23 normal) from patients with gastric adenocarcinoma in Para, Brazil (2017 to 2020). RNA was extracted, quality checked, and used for cDNA library preparation (TruSeq, Illumina). Sequencing was performed on NextSeq 500, followed by quality control (FastQC), trimming (Trimmomatic), and quantification (Salmon, hg38/GENCODE v.42). Differential expression was assessed with DESeq2 in R. A panel of 304 epigenetic genes was examined, and expression patterns were visualized through heatmaps and clustering. Among the 304 genes analyzed, 167 (55%) showed differential expression in GC compared with normal tissue. Of these, 17 were related to DNA methylation, 29 to RNA methylation, 34 to histone acetylation, and 87 to histone methylation. Our results demonstrate dysregulation of all epigenetic processes investigated, promoting the activation of oncogenes (DNMT1, MYC, ELF3, HDAC4, and HDAC7) and the silencing of tumor suppressors (CTCF, DNMT3B, ATRX, PRDM16 and MSH6), promoting genomic instability, apoptosis evasion, and tumor progression. No standard activation or repression patterns were found. Distinct and specific tumor profiles highlight the central role of epigenetic mechanisms in the pathogenesis of GC. Furthermore, epigenetic regulators have been shown to be potential biomarkers, prognosticators, and therapeutic targets.