Abstract
BackgroundOxidative stress induces various intracellular damage, which might be correlated with tumorigenesis. Accumulated oxidative stresses might inactivate protein tyrosine phosphatase (PTP) by oxidizing it, and inducing the phosphorylation of H2AX (γH2AX) in response to DNA damage.MethodsWe evaluated the clinical significance of the expression of oxidized-PTP and γH2AX in 169 gastric carcinomas.ResultsImmunohistochemical expression of nuclear oxidized-PTP, cytoplasmic oxidized-PTP, and γH2AX expression were significantly associated with each other, and their expressions predicted shorter survival of gastric carcinoma patients. In multivariate analysis, nuclear oxidized-PTP (overall survival; p < 0.001, relapse-free survival; P < 0.001) was an independent indicator of poor prognosis of gastric carcinoma patients. In addition, co-expression patterns of nuclear oxidized-PTP and γH2AX were independent indicators of poor prognosis of gastric carcinoma patients (overall survival; P < 0.001, relapse-free survival; P < 0.001).ConclusionsThis study suggests that oxidative stress-mediated oxidation of PTP might be involved in the progression of gastric carcinomas. In addition, this study suggests that individual and co-expression pattern of nuclear oxidized-PTP and γH2AX might be used as a prognostic marker of gastric carcinomas.
Highlights
Oxidative stress induces various intracellular damage, which might be correlated with tumorigenesis
In summary, our results suggest that the accumulation of irreversibly hyper-oxidized protein tyrosine phosphatase (PTP) and γH2AX might be involved in the progression of gastric carcinoma
This study had the limitation that the staining for Ox-PTP could not specify specific PTPs involved in the progression of gastric carcinoma, our results suggest that regulation of PTPs could be potential target for the treatment of gastric carcinoma
Summary
Oxidative stress induces various intracellular damage, which might be correlated with tumorigenesis. Accumulated oxidative stresses might inactivate protein tyrosine phosphatase (PTP) by oxidizing it, and inducing the phosphorylation of H2AX (γH2AX) in response to DNA damage. By regulating the phosphorylation status of various proteins, PTPs are involved in various cellular processes such as cellular proliferation, differentiation, apoptosis, adhesion, motility, Hussein et al BMC Cancer (2018) 18:836 silencing phosphatase activity of PTPs [1, 5]. Continuous exposure to reactive oxygen species (ROS) induces hyper-oxidation of PTPs to form biologically irreversible sulfinic and sulfonic acid states in PTPs [1, 2, 6]. Oxidation of PTPs is common in human cancers and influences tumorigenesis as seen in PTEN inactivation by oxidation [3, 7, 8]. Oncogenic mutation induces ROS production and that enhances mitogenic and mutogenic signaling to contribute to tumor development [9,10,11]
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