Expression And Clinical Impact Of FBP1 In B-cell Non-hodgkin's Lymphomas

Objective1. To investigate the expression of far upstream element binding protein 1(FBP1) in the B-cell Non-Hodgkin's lymphomas(B-cell NHL), and identify the role of FBP1 abnormal expression in the occurrence and development progress of B-cell NHL.2. To explore the effect of FBP1 expression in NHL cell proliferation, cycle regulation and adhesion mediated drug resistance(CAM-DR). To futher reveal the relationship between the expression of FBP1 and the molecular pathogenesis process of B-cell NHL.Methods1. The expression of FBP1 in 80 samples of different types of B-cell NHL and 19 samlples of RL tissue were detected using immunohistochemical. And we analyzed the connection between FBP1 protein level and clinicopathologic datas of B-cell NHL patients, such as age, gender, extranodal sitesand, lactic dehydrogenase(LDH) and so on. And the prognosis date was analyzed with the univariate and multivariate Cox proportional hazards regression analysis.2. The expression of FBP1 in B-cell NHL cell lines Daudi and OCI-LY8 were detected by Western blot. Si RNA target FBP1 was constructed and transiently transfected into Daudi and OCI-LY8 cells. Then flow cytometry, western blotand cell viability assay were used to detect the effect of FBP1 exprssion in cells proliferation, cell cycle regulation process. Furthermore, we cultured NHL cells with fibronectin or stromal cells HS-5 and then treated cells with chemotherapy drug(Doxorubicin, Dox). CaleinAM and cell viability assaies were used to clarify the role of FBP1 in CAM-DR procedure and the concrete molecular mechanisms.Results1. Immunohistochemistry analysis showed that FBP1 expression pattern was different in a variety of B-cell NHL tissues. The FBP1 expression in the invasive NHL cases was higher than the indolent cases. Statistical analysis indicated that FBP1 staining was significantly positive with advanced age(P<0.001), multiple extranodal sites(P=0.025) and the expression of proliferating marker Ki-67(P<0.001). Unvaried analysis displayed that FBP1 high expression was associated with poor prognosis of patients(P<0.001). Multivariate Cox proportional hazards regression analysis indicated that FBP1 expression could bean independent prognostic marker for B-cell NHL(P<0.001).2. FBP1 expressed in both Daudi and OCI-LY8 cell lines. Knockdown of FBP1 by siRNA was found to inhibite the proliferation of NHL cells. The expression of proliferating marker PCNA was also decreaed. It showed that FBP1 knockdown resulted in cell cycle arrested in G1 phase, followed by the descendent level of CDK2, Cyclin A and CyclinD1. Furthermore, our study found that FBP1 was high expressed when NHL cells were cocultured with fibronectin or stromal cells. Down-regulation of FBP1 led to the reversed cell adhesion ability and incremental sensitivity to Doxorubicin of NHL cells.Conclusions1. The expression of FBP1 was upregulated in B-cell NHL and FBP1 was a positively independent prognostic indicator of overall survival. These data revealed that FBP1 may play a role in the oncogenesis and development of B-cell NHL. FBP1 may be a new prognostic marker for B-cell NHL.2. FBP1 might play an important role of cell cycle progress and participate in the development of CAM-DR. Our research would provide a theoretical basis for manufacturing a novel targeted therapeutic for NHL.