Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori

Arab J Gastroenterol. 2023 May;24(2):91-97. doi: 10.1016/j.ajg.2023.01.004. Epub 2023 Jan 29.

Abstract

Background and study aims: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC.

Patients and methods: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n = 35, IM group n = 45, control group n = 25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software.

Results: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p < 0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p < 0.05).

Conclusion: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.

Keywords: Gastric cancer; Gene expression; Helicobacter Pylori; Intestinal metaplasia; WNT signaling.

MeSH terms

  • Case-Control Studies
  • Dishevelled Proteins / metabolism
  • Gastric Mucosa / metabolism
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / genetics
  • Helicobacter pylori*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
  • Risk Factors
  • Stomach Neoplasms* / pathology
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • RHOA protein, human
  • rhoA GTP-Binding Protein
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • DVL2 protein, human
  • Dishevelled Proteins