Prediction of progression of chronic atrophic gastritis withHelicobacter pyloriand poor prognosis of gastric cancer by CYP3A4

Abstract

Background and Aim It has been well documented that Helicobacter pylori (H. pylori) infection is a risk factor for aggravating gastric mucosal atrophy. However, the exact molecular mechanism mediating this process is not fully elucidated. The purpose of this study was to identify biomarkers, which may predict the risk for progression of chronic atrophic gastritis (CAG) with H. pylori. Methods GSE27411 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) between H. pylori‐infected samples without CAG and H. pylori‐infected CAG samples were analyzed. Gene Ontology and pathway enrichment analyses were performed, followed by protein–protein interaction network construction. We used immunohistochemistry analysis to identify DEGs in 20 chronic gastritis, 20 CAG, and 22 gastric cancer (GC) specimens. Results A total of 303 upregulated and 26 downregulated DEGs were identified. The pathways enriched by upregulated DEGs were mainly related to fat digestion and absorption, peroxisome proliferator‐activated receptor signaling pathway, and chemical carcinogenesis. Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) had the highest degrees in protein–protein interaction network. Moreover, the positive rates of CYP3A4 protein expression in chronic gastritis, CAG, and GC were 10% (2/20), 55% (11/20), and 77.3% (17/22), respectively (P < 0.001). The Kaplan–Meier analysis revealed that elevated expression of CYP3A4 was significantly associated with worse overall survival and first progression, respectively (P < 0.0001). Conclusion According to the findings of this study, the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC. Therefore, CYP3A4 may be biomarkers to predict progression of CAG and poor prognosis of gastric cancer.

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“…These data support the CYP2J2 expression trend observed in other cancerous tissue samples [3]. Interestingly, a new report showed that elevated expression of CYP3A4 could be associated with the progression of chronic atrophic gastritis to gastric cancer and might predict poor prognosis [50]. A recent study has shed some light on the role of CYP2E1 in the development and progression of gastric adenocarcinoma [51].…”

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“…In addition to liver cancer, the dysregulation of CYP3A4 was also found in gastric cancer samples compared with chronic atrophic gastritis cases, which indicates a correlation between CYP3A4 expression and carcinogenic transformation of gastric cancer. 40 Moreover, a similar trend was explored in the influence of CYP2C9 expression. The hepatic CYP2C9 proteins account for nearly 20% of CYP content, and CYP2C9 functions as a major enzyme that participates in the metabolism of various drugs, 41 including warfarin, non-steroidal anti-inflammatory drugs, phenytoin, etc..…”

Exploring the Molecular Mechanism of Astragali Radix-Curcumae Rhizoma against Gastric Intraepithelial Neoplasia by Network Pharmacology and Molecular Docking

“…CYP3A4 and CYP1A1 are members of the cytochrome P450 superfamily of enzymes. A recent study found that the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC, which may be biomarkers to predict the progression of CAG and the poor prognosis of GC [ 42 ]. As an isoenzyme of the CYP family I, CYP1A1 mainly participates in the oxidative conversion of the xenobiotics.…”