Inverse expression of ubiquitin-specific peptidase 19 and caspase 7 correlates with gastric neoplastic transformation

Ubiquitin-specific protease 19 (USP19) is a deubiquitinylase (DUB) that is part of the USP family, the largest group of DUBs in humans. Growing evidence has indicated that USP19 is involved in tumor progression and serves as a new prognostic marker for various malignant disorders. Interestingly, USP19 has been shown to have both promoting and inhibiting effects on the onset and development of different neoplasms, depending on the specific tissue type. DUBs including USP19 affect a variety of cell functions including apoptotic cell death. Herein, caspase 7 acts as a key executioner in apoptosis, and its expression levels serve as a prognostic and diagnostic marker in various cancers. This study analysed the expression of USP19 and caspase 7 in gastric pathology along the progression of stomach cells to gastric adenocarcinoma (Correa cascade). We analysed the expression and subcellular localization of USP19 and caspase 7 by immunohistochemistry (IHC) in 296 paraffin-embedded human gastric tissue samples. The cohort included various gastric conditions such as autoimmune gastritis (A-gastritis), Helicobacter pylori gastritis (HP-gastritis), chemical gastropathy (C-gastritis), adenoma, and adenocarcinoma, using gastric mucosa without pathological changes as a reference point. We observed a significant upregulation of USP19 expression in HP-gastritis, adenoma and adenocarcinoma. In contrast, caspase 7 was significantly upregulated in A-gastritis and HP-gastritis and significantly downregulated in both adenoma and adenocarcinoma. USP19 and caspase 7 showed distinct expression patterns across different gastric pathologies. Both USP19 and caspase 7 overexpression maybe associated with inflammation, while USP19 overexpression and no caspase 7 expression could indicate neoplastic transformation. This inverse expression may help distinguish early and late neoplastic epithelial changes in chronic gastritis.