PRDX4 overexpression is associated with poor prognosis in gastric canceropen access
- 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
- Issue Date
- SPANDIDOS PUBL LTD
- stomach neoplasm; peroxiredoxin IV; biomarkers; prognosis; survival analysis
- ONCOLOGY LETTERS, v.19, no.5, pp.3522 - 3530
- Journal Title
- ONCOLOGY LETTERS
- Start Page
- End Page
- 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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- College of Medicine > Department of Medicine > Journal Articles
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