1. Department of Oncology, Affiliated Tumor Hospital of Nantong University, No.30 Tongyang North Road, Nantong 226361, China.
2. Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong.
3. Department of Pathology, Tumor Hospital Affiliated to Nantong University, Nantong, China.
*These authors contributed equally to this work.
Background: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Previous studies have shown that PRDM5 is methylated and silenced in GC. However, the role of PRDM5 in GC progression has not been explored.
Methods: The expression and epigenetic alterations of PRDM5 in GC were analyzed in public datasets. The mRNA and protein expression of PRDM5 in fresh tissues were detected by semi-quantitative PCR and Western blot. And expression of PRDM5 in gastric paracarcinoma and carcinoma tissues from 162 patients was detected by immunohistochemistry (IHC) and assessed the association with different clinicopathological features. The prognostic value of PRDM5 in GC patients was evaluated using Kaplan-Meier plotter. We also studied promoter region methylation of PRDM5 in GC by methylation-specific PCR (MSP). The effects of PRDM5 on cell proliferation and migration were conducted by functional experiments in vitro.
Results: The expression of PRDM5 was downregulated in GC, and that was associated with poor survival and tumor progression. And PRDM5 expression was found to be an independent prognostic factor for GC. We also found that the methylation of PRDM5 promoter was closely related to the histopathological types and the progression of tumors through the public relations database. In vitro, ectopical expression of PRDM5 inhibited the growth of tumor cells, while knockdown of PRDM5 increased the proliferation and migration of tumor cells.
Conclusion: These results suggest that PRDM5 may be a novel TSG methylated in GC that plays important roles in GC development. And we found PRDM5 as a potential survival biomarker for GC, especially in well differentiated GC. PRDM5 expression was significantly correlated with tumor stage and histological type.
Keywords: GC, Promoter methylation, PRDM5, proliferation, prognosis