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Pretreatment Serum Level of Osteopontin and Vascular Endothelial Growth Factor Might Have a Prognostic Value in Patients with Diffuse Large B-Cell Lymphoma

Angiogenesis is gaining importance in hematological malignancies ; it is regulated by a balance of various enhancing and inhibiting angiogenic factors. However, studies related to the prognostic value of angiogenic factors and aggressive Non-Hodgkin lymphomas are limited compared to solid tumors. The aim of this study was to determine pretreatment serum level of vascular endothelial growth factor (VEGF) and osteopontin (OPN) in patients with diffuse large B cell lymphoma (DLBCL) and to investigate whether these factors provide prognostic information. We measured pretreatment serum levels of VEGF and OPN by Enzyme-Linked Immunosorbent Assay (ELISA) in 67 patients newly diagnosed as diffuse large B-cell lymphoma and in 30 healthy controls. All patients were treated with rituximab-CHOP chemotherapy. The serum OPN levels were found elevated in untreated DLBCL patients compared to controls: in newly diagnosed patients it ranged from 25 to 238 pg/ml ; median 94.2 pg/ml while in the healthy controls it ranged from 13 to 46.5 pg/ml ; median 30.0 pg/ml (P=0.00008). There were significant differences in the serum VEGF levels between DLBCL patients and controls (median 480.96 pg/ml vs. 163.8 pg/ml, P=0.001). Serum OPN levels higher than the median level were related to advanced Ann Arbor stage (P=0.026), International Prognostic Index of 2 or higher (P=0.005), ECOG III-V (P=0.004). The complete remission rate after treatment was higher in patients with low OPN serum levels than in those with high OPN serum levels (67.5% versus 32.4%, P=0.002). Elevated serum levels of OPN were strongly associated with shorter overall survival (P=0.007) and event-free survival (P=0.04). In multivariate analysis with International Prognostic Index criteria, OPN remained a significant predictor for overall survival (P=0.033). VEGF level was significantly correlated with age (P=0.01) and serum lactate dehydrogenase level (P=0.02), but not strongly correlated with other potential prognostic factors, and it failed to show prognostic significance. Our results showed that pretreatment serum level of OPN is significantly related to outcome in DLBCL patients. Ongoing extension study and additional follow-up will provide more information moving forward.

VEGF; Osteopontin; lymphoma; angiogenesis

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