EMAP II Expression Is Increased on Peripheral Blood Cells from Non-Hodgkin Lymphoma

Abstract

Tumor immune evasion is a lineament of cancer. Endothelial monocyte activating polypeptide-II (EMAP II) has been assumed to impact tumor immune escape significantly. EMAP II was first reported in the murine methylcholanthrene A-induced fibrosarcoma supernatant and identified as a tumor-derived cytokine. This study evaluated EMAP II expression in peripheral blood cells and its association with treatment outcome, lactate dehydrogenase (LDH) levels, and clinical criteria in non-Hodgkin's lymphoma (NHL) patients. EMAP II expression on different blood cells obtained from the peripheral blood of 80 NHL patients was evaluated by two-color flow cytometry. The study reported that EMAP II expression was significantly increased in peripheral blood cells in patients with NHL compared to normal volunteers (P < 0.001). Additionally, EMAP II expression levels on blood cells decreased in complete remission (CR) while they increased in relapse. This study showed coexpression of EMAP II and CD36 on peripheral lymphocytes in NHL patients but not in healthy controls (P < 0.001). EMAP II expression on blood cells was associated with increased serum LDH levels. Furthermore, the percentages of EMAP II+/CD36+ peripheral lymphocytes were significantly higher in relapse than in CR and healthy controls. Analyses revealed that higher percentages of EMAP II+CD36+ cells were positively correlated with hepatomegaly, splenomegaly, and an advanced (intermediate and high risk) NHL stage. The results assume that EMAP II might be involved in NHL development and pathogenesis.

Figure 1

EMAP II is expressed on peripheral blood cells in NHL patients and normal controls. The cells were stained with FITC-labeled, PE-labeled and PerCP-Cy5.5-labeled antibodies. (a) Newly diagnosed NHL patients. (b) Patients with CR. (c) Patients with recurrence. (d) Flow cytometric dot plots of normal control.

Figure 2

EMAP II expression in CD3, CD5, CD7, and HLA-DR cells: (a) newly diagnosed NHL patient; (b) representative flow cytometric dot plots of normal control.

Figure 3

Flow cytometric detection of CD36 in EMAP+ lymphocytes. (a) NHL patient has not received treatment yet. (b) NHL patients achieved CR. (c) Patients with disease relapse. (d) Normal control.

Figure 4

Correlations between EMAP II percentages on peripheral blood cells in NHL patients. P values are shown.

Figure 5

Diagnostic performances of percentages of EMAP II+CD4, EMAP II+CD8+, EMAP II+CD16+, EMAP II+CD20+, and EMAP II+CD22+ for identifying NHL patients with recurrence. (a) ROC curves were gained by curves at different cut-offs for NHL patients. (b) AUC (area under the curve) with cut-offs, sensitivity, and specificity for the markers. Significance (P < 0.05) is identified with ^∗. High statistical significance (P < 0.001) is identified with ^∗∗.

Figure 6

Diagnostic performances of percentages of EMAP II+CD4, EMAP II+CD8+, EMAP II+CD16+, EMAP II+CD20+, and EMAP II+CD22+ for identifying NHL patients with complete remission. (a) ROC curves were gained by curves at different cut-offs for NHL patients. (b) AUC (area under the curve) with cut-offs, sensitivity, and specificity for the markers. High statistical significance (P < 0.001) is identified with ^∗∗.