Int J Med Sci 2019; 16(9):1199-1206. doi:10.7150/ijms.36071

Research Paper

The impact of PRDX4 and the EGFR mutation status on cellular proliferation in lung adenocarcinoma

Kenichi Mizutani1, Xin Guo1✉, Akihiro Shioya1, Jing Zhang1, Jianbo Zheng1, Nozomu Kurose1, Hiroaki Ishibashi2, Nozomu Motono3, Hidetaka Uramoto3, Sohsuke Yamada1

1. Departments of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
2. Departments of Oral and Maxillofacial Surgery, Kanazawa Medical University, Ishikawa, Japan.
3. Departments of Thoracic Surgery, Kanazawa Medical University, Ishikawa, Japan.

Abstract

Background: Oxidative stress plays key roles in the progression of lung adenocarcinoma. Recently, we reported that peroxiredoxin 4 (PRDX4), an antioxidant enzyme, can be a prognostic marker of lung adenocarcinoma (LUAD). In the present study, we aimed to further investigate the relationship among the PRDX4 expression, epidermal growth factor receptor (EGFR) mutations and cell proliferation in LUAD.

Methods: The expression of PRDX4 was immunohistochemically analyzed and the EGFR mutation status was examined in 127 paraffin-embedded human surgical specimens from patients with stage I LUAD. The PRDX4 expression was considered to be high when >40% of the adenocarcinoma cells were positively stained. In vitro, using plasmid transfection methods, PRDX4 plasmid DNAs were transfected into human lung adenocarcinoma cell lines, A549 (EGFR-wild) or PC-9 (EGFR mutant). The viability of these cells was analyzed using a Cell Counting Kit-8 kit.

Results: The number of cases with high PRDX4 expression levels among patients with LUAD with EGFR mutations was significantly larger than that in patients with EGFR wild-type. The combination of the PRDX4 expression level with the EGFR mutation status was closely associated with the prognosis of patients with stage I LUAD. Viability assays showed that the proliferation of A549 cells was significantly suppressed after PRDX4 plasmid transfection, while the overexpression of PRDX4 had no effect on the proliferation of EGFR-mutant PC-9 cells.

Conclusions: The PRDX4 expression and EGFR mutation status were significantly associated with the prognosis of patients with stage I LUAD, and EGFR mutations affected the role of PRDX4 in the proliferation of LUAD cells.

Keywords: PRDX4, EGFR, cell proliferation, prognosis, lung adenocarcinoma (LUAD).

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How to cite this article:
Mizutani K, Guo X, Shioya A, Zhang J, Zheng J, Kurose N, Ishibashi H, Motono N, Uramoto H, Yamada S. The impact of PRDX4 and the EGFR mutation status on cellular proliferation in lung adenocarcinoma. Int J Med Sci 2019; 16(9):1199-1206. doi:10.7150/ijms.36071. Available from http://www.medsci.org/v16p1199.htm