Overexpression of peroxiredoxin-3 and -5 is a potential biomarker for prognosis in endometrial cancer

Abstract

Endometrial cancer is the sixth most common cancer in women worldwide. Peroxiredoxins (PRDXs) are antioxidant enzymes that serve important roles in cell differentiation, proliferation, and apoptosis. In the present study, the potential associations between PRDX expression and endometrial cancer were investigated. The expression levels of various PRDX mRNAs were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in endometrial cancer tissues (n=26) and normal endometrial tissues (n=10). Additionally, the expression of PRDX isoforms was immunohistochemically examined in endometrial cancer tissues and adjacent normal endometrial tissues from 42 patients. Finally, the associations between high PRDX expression levels and clinicopathological features were examined in patients with endometrial cancer. Analysis of PRDX expression in endometrial cancer tissues and normal endometrial tissues by semi-quantitative RT-PCR showed that all PRDX isoforms had increased expression in the endometrial cancer tissues compared with that in the normal endometrium, and the differences in the expression levels of PRDX1 and PRDX3 between cancer and normal tissues were statistically significant (P=0.0015 and P=0.0134, respectively). Additionally, analysis of PRDX expression in endometrial cancer and paired normal endometrial tissues by immunohistochemistry showed strong cytoplasmic staining of PRDX3 and PRDX5 in cancer tissues, with high PRDX3 (25/42, 59.5%) and PRDX5 (32/42, 76.2%) appearing more frequently in endometrial cancer than in normal endometrial tissues (P=0.0001 and P=0.0023, respectively). Furthermore, high expression of PRDX5 was associated with advanced-stage endometrial cancer (P=0.0399). Although the 5-year survival rate was marginally higher in patients with low expression of PRDX3 and PRDX5, this result was not statistically significant. In summary, PRDX3 and PRDX5 are highly expressed in endometrial cancer and could be associated with advanced stage and poor prognosis. Therefore, these proteins may potentially be used as prognostic markers for endometrial cancer.

Keywords: endometrial cancer; peroxiredoxin; prognostic marker.

Figure 1.

PRDX mRNA expression in endometrial cancer and normal endometrial tissues from benign uterine disease, as determined by semi-quantitative reverse transcription-polymerase chain reaction. All values represent the mean ± standard deviation (bars) of three samples in independent experiments, which were repeated three times with similar results. *P<0.05. PRDX, peroxiredoxin.

Figure 2.

Immunohistochemical staining for (A) PRDX3 (magnification, ×200) and (B) PRDX5 (magnification, ×100) in endometrial cancer (arrow) and adjacent normal endometrial glands (star). PRDX, peroxiredoxin.

Figure 3.

Survival rates of patients with endometrial cancer according to PRDX3 and PRDX5 expression levels. Kaplan-Meier survival curves showing cumulative survival rates of patients with (A) high or low PRDX3 expression, and (B) high or low PRDX5 expression. Percentages in brackets indicate the survival rate at 5 years. The results indicate that patients with endometrial cancer in the high PRDX3 and PRDX5 expression groups had a decreased 5-year survival rates compared with those in the low PRDX3 and PRDX5 expression groups. However, the associations between survival and PRDX expression were not statistically significant (P=0.2971 and P=0.3818, respectively). PRDX, peroxiredoxin.