Clinical significance of chemokine receptor CXCR4 and mammalian target of rapamycin (mTOR) expression in patients with diffuse large B-cell lymphoma

To assess the relevance of C-X-C chemokine receptor type 4 (CXCR4) and mammalian target of rapamycin (mTOR) to large-B-cell lymphoma (DLBCL), levels of protein expression were measured in 56 DLBCL patients who had received rituximab-based therapy. Of these, 34 were positive for CXCR4 expression (60.7%) and 31 for mTOR (55.4%). CXCR4 expression was positively correlated with mTOR expression (r=0.602; p=.000). CXCR4 expression was significantly associated with high lactate dehydrogenase (LDH) level (p=.009), high IPI score (p=.030) and non-GCB subtype (p=.006). Furthermore, the expression levels of CXCR4 and mTOR were negatively correlated with the chance of remission (p<.05). Kaplan-Meier analysis indicated significantly shorter progression-free survival (PFS) and overall survival (OS) in patients positive for CXCR4 and mTOR expression. The combination therapy with CXCR4 inhibitor WZ811 and mTOR inhibitor everolimus showed syncergistic effect in DLBCL cell lines. These results suggest that the expression of CXCR4 and mTOR may be suitable as biomarkers of the prognosis of DLBCL and for development of new therapeutic strategies.