Identification and verification of PRDX1 as an inflammation marker for colorectal cancer progression

Am J Transl Res. 2016 Feb 15;8(2):842-59. eCollection 2016.

Abstract

Chronic inflammation contributes to high risk of colorectal cancer (CRC) development. Thus, discovering inflammation biomarkers for monitoring of CRC progression is necessary. In this study, we performed isobaric tags for relative and absolute quantitation-based proteomic assay on CRC tissues and paired normal mucosal tissues to identify key components in CRC pathogenesis. A total of 115 altered protein expressions were found with over twofold difference as compared with normal controls, which were associated with various molecular functions and biological processes. Here, we found that peroxiredoxin 1 (PRDX1) expression was higher in CRC tissues than that of matched controls and was determined as a tumor biomarker by receiver operating characteristic curve. PRDX1 expression was significantly upregulated in NCM460 cells challenged by H2O2 in a dose-dependent manner. PRDX1 depletion in SW480 cells enhanced reactive oxygen species (ROS), NO, and ONOO(-) production and increased the mRNA and protein expressions of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, and IL-6] and chemokines (IL-8 and CXCL1), and partly activated nuclear factor-κB p65. Overall, our findings provide data on global alteration in the proteome of CRC tissues and reveal the potential of PRDX1 as an inflammation marker in CRC development, suggesting a novel therapy against inflammation-associated CRC.

Keywords: Colorectal cancer; PRDX1; biomarker; iTRAQ; inflammation.