PRDX4 Potentially Serves as an Independent Marker for Early Recurrence of Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC), a main histological subtype of oral cavity cancer, remains one of the most prevailing tumors worldwide with the increasing incidence and mortality. Since a high rate of early local recurrence is one of the major risk factors for poor outcome of OSCC, its prognostic biomarkers are urgently needed. Peroxiredoxin 4 (PRDX4), a member of PRDXs, which are involved in the antioxidant defense, is a unique secreted subtype of PRDXs. A certain number of previous studies have disclosed that the overexpression of the PRDX4 protein has a clear relationship with tumor initiation and progression in many cancers. Furthermore, recent studies have revealed that PRDX4 promotes tumor development through the Wnt/β-catenin signaling pathway.

To assess the status of the PRDX4/β-catenin expression and its association with clinical outcomes, including early local recurrence in OSCC, we immunohistochemically examined PRDX4 expression levels and cytoplasmic β-catenin protein accumulation levels in a total of 72 postoperative OSCC samples.

The immunohistochemically high expression of PRDX4 was significantly correlated with poorer early phase 2-year recurrence-free survival (RFS), associated closely with higher PRDX4 expression levels especially the OSCC nests of invasive fronts or perineural invasion. In addition, a multivariate Cox regression analysis revealed that PRDX4 was an independent prognostic factor for 2-year RFS. Moreover, high β-catenin accumulation is significantly associated with distant metastasis. A comparison of the combination of a high expression of PRDX4 and high β-catenin protein accumulation groups with the other groups only showed a significant predominance among men.

The increased expression of PRDX4 may be a useful independent prognostic biomarker for recurrence of OSCC, especially in the early postoperative phase.