| ObjectiveThe expression and impact of hypoxia-inducible factor has not yet been reported in diffuse large B-cell lymphoma, this study was want to detect the expression and relationship of HIF-2a, FOXP3 and NF-k B in DLBCL, analysis of their impact on prognosis in order to explore the role of hypoxia in DLBCL, provided theoretical basis for exploring new therapeutic approaches of DLBCL. MethodThis retrospective study included 90 patients with diffuse large B-cell lymphoma(DLBCL) newly diagnosed between January 2011 and November 2014 at Tian Jin Medical University Cancer Center of China. Tissue sections will be selected specimens, and detect the expression of HIF-2a, FOXP and NF-k B in the lymph node tissue paraffin blocks of 90 patients using immunohistochemistry. Univariate analysis using Long-rank test,multivariate analysis was performed using a Cox proportional hazards model(stepwise backwards and forwards methods) including IHC parameters and clinical factors in the International Prognostic Index with prognostic significance in univariate analysis. P values <0.05 are considered statistically significant. Using Spearman correlation analysis to describe the relationship betweent HIF-2α and FOXP3,HIF-2α and NF-κB, Categorical variables were compared use chi-square test and P value of less than 0.05 were considered to be statistically significant. All statistical analyses were performed using SPSS version 18.0 statistical software(SPSS, Inc., Chicago, IL). Result1.The expression of HIF-2α was 57.8%, the expression of FOXP3 was 45.6% and the expression of NF-k B was 31.1% in 90 cases of DLBCL patients.2.HIF-2a LDH high expression levels were significantly higher(P <0.005); FOXP3 expression of rituximab group had a better response(P <0.005); NF-k B high expression of origin from Non-Germinal center B cells(Non-GCB)(P <0.005).3.There is a negative correlation between the expression of HIF-2α and FOXP3(P <0.005).4. 3-year overall survival rate of HIF-2a negative group and 3-year disease-free survival rates were better than the positive group(P <0.005).5.3-year OS and PFS FOXP3-positive 3-year group were better than negative group(P <0.005).6. 3-year PFS of NF-k B negative better than positive group(P <0.005).7.Multivariate analysis showed that IPI score(P=0.043), HIF-2a(P=0.015) and FΟΧP3(P=0.009) is the independent prognostic factors for OS, while the FΟΧP3(P=0.016) and β2-microglobulin(P=0.025) is the independent prognostic factors for PFS. ConclusionWe detected the expression of HIF-2a, FOXP3 and NF-k B protein in diffuse large B-cell lymphoma. And the expression of HIF-2a, FOXP3 and NF-k B had a closely related with prognosis, in which HIF-2a is an independent adverse prognostic factors of DLBCL. This may means that the hypoxic tumor microenvironment has a closely related with prognosis in diffuse large B-cell lymphoma. |
