The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis

Abstract

Previous reports indicated that prion protein (PrP) is involved in gastric cancer (GC) development and progression, but its role in GC prognosis has been poorly characterized. A total of 480 GC patients were recruited in this retrospective study. PrP expression in cancerous and non-cancerous gastric tissues was detected by using the tissue microarray and immunohistochemical staining techniques. Our results showed that the PrP expression in GC was significantly less frequent than that in the non-cancerous gastric tissue (44.4% vs 66.4%, P < 0.001). Cox regression analysis revealed that PrP expression was associated with TNM stage, survival status and survival time. GC patients with higher TNM stages (stages II, III and IV) had significantly lower PrP expression levels in tumors than those with lower TNM stages (stages 0 and I). Kaplan-Meier survival curves revealed that negative PrP expression was associated with poor overall survival (log-rank test: P < 0.001). The mean survival time for patients with negative PrP expression was significant lower than those with positive PrP expression (43.0±28.5m vs. 53.9±31.1m, P<0.001). In multivariate Cox hazard regression, PrP expression was an independent prognostic factor for GC survival, with a HR (hazard ratio) of 0.687 (95%CI:0.520-0.907, P=0.008). Our results revealed that negative PrP expression could independently predict worse outcome in GC and thereby could be used to guide the clinical practice.

Physiological Functions of the Cellular Prion Protein

“…Indeed, Chieng and Say (2015) found that overexpression of PrP C in a colon adenocarcinoma cell line increased invasiveness, whilst a study of pancreatic ductal adenocarcinoma patients reported that PrP C -positive tumours were associated with reduced survival time from diagnosis (Sy et al, 2011). PrP C expression was also shown to be upregulated in cancerous tissue from human gastric cancer patients compared with adjacent non-cancerous tissue from the same individuals (Zhou et al, 2014), although a recent study of a larger patient group found the opposite correlation (Tang et al, 2016). …”

The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

“…Cancer is the second leading cause of death worldwide. Studies in recent years show that PrP C is involved in various aspects of cancer biology such as cell proliferation, metastasis, cell death, drug resistance and cancer stem cells (14)(15)(16)(17)(18)(19)(20)(21). In this review, we summarize the current progress in these aspects.…”

The Role of Cellular Prion Protein in Promoting Stemness and Differentiation in Cancer

“…As recently reported, PrP C is highly expressed in a variety of solid tumors, including gastric and colorectal cancer [ 25 , 26 , 27 , 28 , 29 ], breast cancer [ 30 , 31 , 32 ], prostate cancer [ 33 ], pancreatic ductal adenocarcinoma (PDAC) [ 34 , 35 , 36 ], lung adenocarcinoma [ 37 ], head and neck squamous cell carcinoma (HNSCC) [ 38 ], osteosarcoma [ 39 ], and melanoma [ 40 , 41 ]. Again, PrP C over-expression is closely associated with tumor malignancy and poor prognosis [ 42 , 43 , 44 , 45 ].…”

“…Recently, PrP C emerged as a potential biomarker in the follow-up of patients following surgical resection of PDAC [ 36 ]. Thus, PrP C may become a useful tool in monitoring the therapeutic efficacy as well as predicting the outcome of cancer patients undergoing chemo- and radiotherapy [ 34 , 44 , 54 , 55 , 56 ].…”