International Journal of Medical Sciences

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22 April 2019

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Int J Med Sci 2018; 15(10):1025-1034. doi:10.7150/ijms.25734

Research Paper

The Combination Of Weak Expression Of PRDX4 And Very High MIB-1 Labelling Index Independently Predicts Shorter Disease-free Survival In Stage I Lung Adenocarcinoma

Akihiro Shioya1, Xin Guo1, Nozomu Motono2, Seiya Mizuguchi3, Nozomu Kurose1,3, Satoko Nakada1,3, Akane Aikawa1,3, Yoshitaka Ikeda4, Hidetaka Uramoto2, Sohsuke Yamada1,3✉

1. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa.
2. Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa.
3. Department of Pathology, Kanazawa Medical University Hospital, Ishikawa.
4. Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, Saga, Japan.


Background: Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD.

Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining.

Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects.

Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients.

Keywords: lung adenocarcinoma (LUAD), stage I, PRDX4, MIB-1, recurrence.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Shioya A, Guo X, Motono N, Mizuguchi S, Kurose N, Nakada S, Aikawa A, Ikeda Y, Uramoto H, Yamada S. The Combination Of Weak Expression Of PRDX4 And Very High MIB-1 Labelling Index Independently Predicts Shorter Disease-free Survival In Stage I Lung Adenocarcinoma. Int J Med Sci 2018; 15(10):1025-1034. doi:10.7150/ijms.25734. Available from