Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

Abstract

Background: As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers.

Methods: In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization.

Results: High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan-Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC.

Conclusions: In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

Keywords: Bioinformatics analysis; HCC; Interaction network; PRDX family; Prognosis.

Fig. 1

The mRNA expression levels of PRDX1 (a) and PRDX2 (b) in multiple common cancer cell lines were obtained from CCLE database. The dashed line within a box is the mean

Fig. 2

The relative expression of PRDXs in normal and HCC samples (UALCAN and HCCDB database). Boxplot showed the expression of PRDX1 (a) and PRDX2 (b) mRNA in HCC samples relative to normal samples based on TCGA database. The mRNA expression levels of PRDX1 (c) and PRDX2 (d) in different HCC datasets of HCCDB database were analyzed. LIHC: the abbreviation of liver hepatocellular carcinoma in TCGA database. Red: HCC samples; blue: adjacent normal tissue samples; cyan: cirrhotic samples; orange: healthy samples

Fig. 3

The protein levels of PRDXs and the correlations between PRDXs expression and patient prognosis in HCC. The protein levels of PRDX1 (a) and PRDX2 (b) in HCC tissues were compared with that in normal tissues by immunohistochemical staining. Kaplan–Meier Plotter database was utilized to evaluate the correlations between the expression of PRDXs (PRDX1 and PRDX2) and prognosis of HCC patients (c, d)

Fig. 4

PRDXs alterations and biological interaction network in HCC. a The genetic alteration of PRDXs in HCC patients from TCGA were analyzed by c-BioPortal database. The different types of genetic alteration were highlighted in different color. b The network of PRDXs neighbor genes in HCC. PRDX1, PRDX2, PRDX3, PRDX5, and PRDX6 were the seed genes, indicated with thick border. The lighter red color suggested decrease frequency of genetic alteration in HCC

Fig. 5

KEGG pathway enrichment analysis of PRDX1 co-expression genes and miRNA targets of PRDX1 in HCC. a Volcano plot showed the differential expression of genes related to PRDX1 in HCC and a Pearson correlation was used for the correlation analysis. Green: negatively correlated significant genes; red: positively correlated significant genes. b Top 50 positively and top 50 negatively correlated significant genes of PRDX1 were presented in the heat map. c The KEGG pathway enrichment of PRDX1 co-expression genes in HCC was analyzed using Gene Set Enrichment Analysis (GSEA). d The miRNA targets of PRDX1 in HCC. FDR false discovery rate