Abstract
BackgroundPeroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. In addition, previous studies report that PRDXs play critical roles in the occurrence and development of carcinomas. However, few studies have conducted systematic analysis of PRDXs in cancers. Therefore, the present study sought to explore the molecular characteristics and potential clinical significance of PRDX family members in pan cancer and further validate the function of PRDX6 in bladder urothelial carcinoma (BLCA).MethodsA comprehensive analysis of PRDXs in 33 types of cancer was performed based on the TCGA database. This involved an analysis of mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, both the gain and loss of function strategies were used to assess the importance and mechanism of PRDX6 in the cell cycle of BLCA.ResultAnalysis showed abnormal expression of PRDX1-6 in several types of cancer compared to normal tissues. Univariate Cox proportional hazard regression analysis showed that expression levels of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of OS, DSS and PFI, and PRDX2 and PRDX3 with favorable survival. In addition, the expression of PRDX genes were positively correlated with CNV and negatively with methylation. Moreover, analysis based on PharmacoDB dataset showed that the augmented levels of PRDX1, PRDX3 and PRDX6 were significantly correlated with EGFR/VEGFR inhibitor drugs. Furthermore, knocking down of PRDX6 inhibited growth of cancer cells through the JAK2-STAT3 in bladder cell lines.ConclusionsPRDXs are potential biomarkers and therapeutic targets for several carcinomas, especially for BLCA. In addition, PRDX6 could regulate proliferation of cancer cell via JAK2-STAT3 pathway and involve into the process of cell cycle in BLCA.
Highlights
Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth
Univariate Cox proportional hazard regression analysis showed that expression of PRDX1, PRDX4 and PRDX6 were mostly associated with poor survival of overall survival (OS), disease specific survival (DSS) and progression free interval (PFI), and PRDX2 and PRDX3 may be protective factors (Fig. 1C, Additional file 1: Figure S2), such as PRDX1, PRDX4 and PRDX6 were risky factors for bladder urothelial carcinoma (BLCA) of OS, DSS and PFI, while PRDX2 and PRDX3 were protective factors for (See figure on page.) Fig. 2 The genetic alterations of PRDXs and associations with mRNA expression
The results demonstrated that pazopanib, vandetanib, lapatinib and cediranib were associated with PRDX1, PRDX3, PRDX4, PRDX6, which suggested that the PRDXs may be strongly associated with the EGF and VEGF signaling pathway
Summary
Peroxiredoxins (PRDXs) are an antioxidant enzymes protein family involved in several biological functions such as differentiation, cell growth. Peroxiredoxin (PRDX) belongs to a large group of antioxidant enzymes protein family which includes more than 3500 members [1]. Members of this family are characterized by a cysteine residue that is involved in reduction of peroxides [2], which are ubiquitously expressed in most organisms [3]. PRDXs can be classified into three subfamilies based on the number and location of the active cysteine residues and other factors. The family members are involved in several biological processes, such as cell differentiation, metabolism [8], inflammation [9], cellular protection against reactive oxygen species (ROS) [10], embryonic development and cellular homeostasis [11]
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