Peroxiredoxin 4 as an independent prognostic marker for survival in patients with early-stage lung squamous cell carcinoma

Abstract

Objectives: Peroxiredoxin 4 (Prx 4) is a newly emerging antioxidant protein that has been studied in several human cancers. Recently, it was revealed that Prx 4 is highly expressed in human lung cancer and is needed for the promotion of lung cancer progression in vitro. However, there are no clinical data regarding the association of Prx 4 and prognosis in lung cancer.

Materials and methods: The Prx 4 expression state as a prognostic indicator was assessed by immunohistochemical staining in 142 patients with stage II non-small cell lung cancer (NSCLC) who had undergone curative surgery between 2006 and 2010. The association between the degree of Prx 4 expression and several clinicopathologic parameters was then evaluated by statistical analyses.

Results: The degree of Prx 4 expression was associated with histology and recurrence in the overall NSCLC patient group, with the proportion of patients with positive Prx 4 expression significantly higher for the adenocarcinoma subtype (39/70, 56%) than the squamous cell carcinoma subtype (23/72, 32%) (P = 0.004). However, when subgroup analyses according to histopathology were performed in terms of recurrence, positive Prx 4 expression was significantly correlated with higher recurrence rates (P = 0.003) and shorter disease-free survival (DFS) (P = 0.003, hazard ratio = 3.910) in patients with squamous cell carcinoma. In contrast, no meaningful relationship was observed between the level of Prx 4 expression and DFS in the adenocarcinoma subgroup.

Conclusion: Positive Prx 4 expression is significantly correlated with recurrence and shorter DFS in patients with early-stage lung squamous cell carcinoma.

Keywords: Lung cancer; immunohistochemistry; peroxiredoxin.

Figure 1

Representative photomicrographs of Prx 4 immunohistochemical staining in arrayed NSCLC tissues. The left and right columns show samples of adenocarcinoma and squamous cell carcinoma representing (A) 0, negative, (B) 1+, weak, (C) 2+, moderate, (D) 3+, strong immunoreactivity in tumor cells, respectively. Original magnification: ×200. Prx 4 was not expressed in normal alveolar or bronchial epithelial cells. Normal bronchial epithelial cell image (Figure S1), negative and positive control cell images (Figure S2) were provided in supplementary data. NSCLC = non-small cell lung cancer; Prx 4 = peroxiredoxin 4.

Figure 2

Kaplan-Meier plots of DFS according to the different levels of Prx 4 expression in the overall group of NSCLC patients (A), in patients with the adenocarcinoma subtype (B), or in patients with the squamous cell carcinoma subtype (C). The DFS of patients with positive Prx 4 expression (solid line) was significantly shorter than that of patients with negative Prx 4 expression (dotted line) in both the overall NSCLC patient group (A) and the squamous cell carcinoma subgroup (C). However, there was no significant statistical difference in the adenocarcinoma subgroup (B). The P value was obtained using the log-rank test of the difference. (x-axis: months after surgery; y-axis: DFS probability). DFS = disease-free survival; NSCLC = non-small cell lung cancer; Prx 4 = peroxiredoxin 4.