In silico analysis reveals PRDX4 as a prognostic and oncogenic marker in renal papillary cell carcinoma

Alterations in the tumor microenvironment leads to the accumulation of reactive oxygen species (ROS). When in low levels, ROS act as a signaling molecule and contribute to tumor cell proliferation whereas its elevation results in oxidative stress and eventually cell death. It is known that antioxidant systems regulate the ROS levels and thus cell fate. Among these systems, peroxiredoxins (PRDXs) were found to be upregulated in various cancers. However their exact contribution to carcinogenesis is not yet clear. Herein, the expression pattern and prognostic value of PRDXs were explored in cancer setting by using in silico analysis tools and publicly available datasets. Pan-cancer analysis revealed that PRDXs are differentially expressed in normal and tumor tissues. Further analysis showed that higher PRDX4 levels was associated with poor prognosis and clinicopathological and histological features associated with a more aggressive renal papillary cell carcinoma (KIRP) profile. Hypoxia, ER stress and protein folding were shown to be pathways positively correlated with PRDX4 levels. Furthermore, PRDX4 was found to be strong regulator of protein homeostasis. Kaplan-Meier analysis revealed that PRDX4 is a potent prognostic marker in Type 2 KIRP and this might be due to increased ER stress and oxidative stress levels in this subtype. The data suggest that PRDX4 can be used as a prognostic marker for KIRP patients. Its association with more aggressive tumor characteristics also underlines that it might be used for targeted therapy.