PRDX4 overexpression is associated with poor prognosis in gastric cancer

Park,Sun Yi; Lee,Young‑Joon; Park,Jiho; Kim,Tae‑Han; Hong,Soon‑Chan; Jung,Eun‑Jung; Ju,Young‑Tae; Jeong,Chi‑Young; Park,Hee Jin; Ko,Gyung Hyuck; Song,Dae Hyun; Park,Miyeong; Yoo,Jiyun; Jeong,Sang‑Ho

doi:10.3892/ol.2020.11468

PRDX4 overexpression is associated with poor prognosis in gastric cancer

Authors:
- Sun Yi Park
- Young‑Joon Lee
- Jiho Park
- Tae‑Han Kim
- Soon‑Chan Hong
- Eun‑Jung Jung
- Young‑Tae Ju
- Chi‑Young Jeong
- Hee Jin Park
- Gyung Hyuck Ko
- Dae Hyun Song
- Miyeong Park
- Jiyun Yoo
- Sang‑Ho Jeong
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Affiliations: Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, South Gyeongsang 52727, Republic of Korea, Department of Surgery, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam‑do 51472, Republic of Korea, Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, Gyeongsang 52727, Republic of Korea, Department of Anesthesiology, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam‑do 51472, Republic of Korea , Division of Applied Life Science (BK21 Plus), Research Institute of Life Sciences, Gyeongsang National University, Jinju, Gyeongsang 52528, Republic of Korea
Published online on: March 19, 2020 https://doi.org/10.3892/ol.2020.11468
Pages: 3522-3530
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Peroxiredoxin IV (PRDX4) is a multifunctional protein that is involved in cell protection against oxidative injury, regulation of cell proliferation, modulation of intracellular signaling, and the pathogenesis of tumors. We previously conducted a proteomic analysis to investigate tumor‑specific protein expression in gastric cancer. The aim of the present study was to investigate whether PRDX4 could be a marker of poor prognosis in patients with gastric cancer. Immunohistochemistry was used to validate PRDX4 as a prognostic marker for gastric cancer. Short hairpin RNA (shRNA)‑mediated knockdown of PRDX4 expression in AGS cells and MKN28 cells was used for functional studies, and PRDX4 overexpression in PRDX4‑depleted cells was used for knock‑in studies. Based on immunohistochemistry data, TNM stage and PRDX4 were independent prognostic factors in the Cox proportional hazard model (P<0.05). In the survival analysis, the PRDX4‑overexpressing group demonstrated significantly worse survival than the PRDX4‑underexpression group (P<0.01). In vitro, knockdown of PRDX4 expression by shRNA caused a significant decrease in cancer invasion. Conversely, overexpression of PRDX4 in PRDX4‑depleted cancer cells promoted migration and invasion. By measuring the expression of EMT‑related genes, we found that E‑cadherin was increased in shPRDX4 cells compared with control shMKN28 cells, and snail and slug were decreased in shPRDX4‑1 cells compared with sh‑control cells. Furthermore, the expression levels of these genes could be recovered in rescue experiments. In conclusion, the results of the present study suggested that PRDX4 is a marker of poor prognosis in gastric cancer and that PRDX4 is associated with cancer cell migration and invasion via EMT.

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