Upregulation of PTGFRN in Hepatocellular Carcinoma Predicts Poor Prognosis: A Study Based on the TCGA Database

Abstract

Background. The importance of prostaglandin F2 receptor inhibitors (PTGFRN) in the progression of a variety of malignant tumors has been recognized in recent years. So far, no role of PTGFRN in hepatocellular carcinoma (HCC) has been reported. In this study, we focused on the possible mechanisms of PTGFRN in HCC based on the Cancer Genome Atlas (TCGA) data. Methods. The mRNA gene expression data of PTGFRN were downloaded from TCGA database to analyze the expression level of PTGFRN in HCC. According to the human protein atlas database, the expression difference of PTGFRN protein between HCC and adjacent tissues was verified. Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between PTGFRN and clinicopathological characteristics. Kaplan Meier method and Cox proportional hazards model were used to explore the prognostic role of PTGFRN in HCC. The ROC curve was used to evaluate the diagnostic value of PTGFRN in HCC. Gene Set Enrichment Analysis (GSEA) was used to investigate the function of PTGFRN related Gene sets. Finally, obtain the co-expressed genes of PTGFRN through the cBioPortal database, and use the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function enrichment analysis to further explore the role of PTGFRN in HCC regulated related pathways.Results. Analysis of mRNA expression data of 377 HCC patients showed that the expression of PTGFRN was up-regulated in HCC, which was confirmed by immunohistochemistry. The overexpression of PTGFRN was significantly correlated with clinical stage (P = 0.028) and histological grade (P = 0.027). High expression of PTGFRN was associated with poorer overall survival.. Meanwhile, multivariate Cox analysis showed that PTGFRN may be a potential independent risk factor for HCC. GSEA enrichment results showed that the up-regulated PTGFRN phenotype was concentrated in "endocytosis", "oocyte meiosis" and "ERBB signaling pathway". In addition, through the analysis of KEGG and GO pathways, we found that PTGFRN co-expressed genes are mainly involved in extracellular matrix tissue, epithelial-mesenchymal transition, cell adhesion and cell cycle, and PI3K-Akt/NF-kB signaling pathways.Conclusions. PTGFRN is highly expressed in HCC and can be used as an independent predictor of the clinical prognosis of HCC.