Abstract
BackgroundOxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL), although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx), manganese superoxide dismutase (MnSOD) and glutamate-cysteine ligase (GCL) via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL.ResultsStrong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002), a high International Prognostic Index (p = 0.002) and strong Trx (p = 0.011) and GCL (p = 0.0003) expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046) and poor disease-specific survival (p = 0.015). Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049). Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003) and disease-specific survival (p = 0.031) compared with the other patients.ConclusionsThe redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.
Highlights
Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy
We discovered that low immunoexpression of glutamate-cysteine ligase (GCL), Trx and nitrotyrosine was associated with favorable progression-free survival and Trx was significant as regards disease-specific survival
In a recent study [22] we found that high levels of GCL and nitrotyrosine, and low levels of manganese superoxide dismutase (MnSOD) correlated with poor prognosis, but the number of patients with diffuse large B-cell lymphoma (DLBCL) in that study was only 18
Summary
Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL), these results cannot be extrapolated to patient populations undergoing modern treatment modalities. Production of reactive oxygen species (ROS) is common to all aerobic cells, but excessive oxidative stress may lead to variable pathological conditions. The most important factor in the redox environment is the creation and elimination of ROS. These are important cellular mediators and their formation is strictly controlled under physiological circumstances. They are mostly formed in the mitochondria as a by-product of oxygen metabolism. Antioxidants are important in the elimination of ROS, maintaining the normal physiological state [9]
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