High Expression of PRNP Predicts Poor Prognosis in Korean Patients with Gastric Cancer

Abstract

Simple Summary Gastric cancer is a lethal cancer that is prevalent in East Asia. It is critical to secure prognostic markers for monitoring patients with GC. Recently, PRNP, the gene encoding prion protein PrP, has been associated with cell proliferation in diverse cancer types. However, the value of PRNP as a prognostic factor for patients with GC has yet to be inspected. The aim of our study was to inspect PRNP gene expression in terms of a prognostic value in GC by utilizing publicly available large GC cohorts with information on survival and gene expression profiles. As a result, we found that PRNP high- vs. low-expressing patients with GC showed poor survival probability in Korean GC cohorts and that knockdown of PRNP decreased cell viability of GC cells. These findings provide evidence for PRNP as a valuable tool for follow-up in patients with GC. Gastric cancer (GC) has the highest occurrence and fourth-highest mortality rate of all cancers in Korea. Although survival rates are improving with the development of diagnosis and treatment methods, the five-year survival rate for stage 4 GC in Korea remains <10%. Therefore, it is important to identify candidate prognostic factors for predicting poor prognosis. PRNP is a gene encoding the prion protein PrP, which has been noted for its role in the nervous system and is known to be upregulated in various cancers and associated with both cell proliferation and metastasis. However, the value of PRNP as a prognostic factor for Korean GC patients remains unclear. Here, we analyzed the relationship between PRNP expression and survival in three independent datasets for Korean patients with GC as well as the TCGA-STAD dataset. Survival analysis indicates that high levels of PRNP expression are associated with poor overall survival of patients with GC. Gene set enrichment analysis showed that PRNP is associated with epithelial mesenchymal transition and Hedgehog signaling. In addition, proliferation of GC cell lines was inhibited after siRNA-mediated knockdown of PRNP. In conclusion, our study suggests a potential role for PRNP as a candidate prognostic factor for patients with GC.